Clinical Factors Associated with Non-Diabetic Renal Disease in Diabetic Latin American Patients, Histopathological Findings, and Predictive Model

Research Article

Clinical Factors Associated with Non-Diabetic Renal Disease in Diabetic Latin American Patients, Histopathological Findings, and Predictive Model

  • Jennifer Garay 1*
  • Jorge Pinilla 1
  • Luis F. Arias 3
  • Mauricio Restrepo 4
  • José M. Ustariz 2
  • Ligia L. Calderón
  • Joaquín Rodelo 2,5

*Corresponding Author: Jennifer Garay, Division of Nephrology, University of Antioquia, Medellin, Colombia.

Citation: Jennifer Garay., Jorge Pinilla., Luis F. Arias., Mauricio Restrepo., José M. Ustariz., et all (2023), Clinical Factors Associated with Non-Diabetic Renal Disease in Diabetic Latin American Patients, Histopathological Findings, and Predictive Model, International Journal of Clinical Nephrology. 5(2); DOI:10.37579/2834-5142/047

Copyright: © 2023, Jennifer Garay. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 17 January 2023 | Accepted: 11 May 2023 | Published: 23 May 2023

Keywords: diabetes mellitus; kidney biopsy; diabetic nephropathy; non-diabetic renal disease; focal segmental glomerulosclerosis; iga nephropathy; acute tubulointerstitial nephritis

Abstract

The prevalence of diabetes was reported by the World Health Organization from 180 million in 1980 to 422 million in 2014, differentiating those patients who have diabetes but it is not the cause of kidney damage and is actually in the presence of non-diabetic renal disease (NDRD) or who, in addition to having diabetic nephropathy, simultaneously suffer from another illness that is aggravating kidney function and is susceptible to a therapeutic intervention other than glycemic control that allows improving renal survival. 

The present analysis of 201 biopsies from native kidneys in diabetes mellitus patients from the pathology department of the University of Antioquia at the San Vicente Hospital clinical laboratory was a retrospective cohort study. The kidney biopsy report that 41% of patients had diabetic nephropathy, 16% mixed, and 43% NDRD, the most frequent histological finding was focal segmental glomerulosclerosis; in the univariate and multivariate analysis, two independent predictors were identified, each year above the mean age (56 years) increases the risk of presenting NDRD (OR, 1.05; 95% CI, 1.02–1.09; p = 0.002) in the KB. Diabetic retinopathy significantly decreases the occurrence of NDRD (OR, 0.23; 95% CI, 0.09–0.60; p = 0.002). Our findings on the potential predictive strategies, the model with the clinical variables age, diabetic retinopathy, and time of diabetes offered the best predictive performance. The area under the discrimination curve was 0.75 (95% CI, 0.67-0.81) with an acceptable Hosmer Lemeshow test, and calibration can be useful when deciding whether to perform a kidney biopsy.

Introduction

The dramatic increase in the prevalence of diabetes reported by the World Health Organization from 180 million in 1980 to 422 million in 2014, plus the high projected growth for 2050 in low and middle-income countries (1, 2) and the association with cardiovascular outcomes, chronic kidney disease (CKD) and mortality (3,4,5), support the interest in differentiating those patients who have diabetes. Still, it is not the leading cause of kidney damage among those with non-diabetic renal disease (NDRD) or who, in addition to diabetic nephropathy, simultaneously suffer from other illnesses that are aggravating kidney function and are susceptible to a therapeutic intervention other than glycemic control that allows improvement in renal outcomes (6,7).

To be able to discriminate diabetic kidney disease, which is a clinical diagnosis, from diabetic nephropathy (DN) alone or combined with another kidney pathology (mixed), is only possible by a kidney biopsy (KB) (8,9). Still, given the risk of the procedure, the clinician’s skill is required to define the patients who benefit from an invasive diagnostic test. The indications described in the literature for type 1 diabetes mellitus include microhematuria, absence of diabetic retinopathy, unusual alteration of renal function or immunological alterations (10), and for type 2 diabetes mellitus are the sudden onset of proteinuria, proteinuria in the absence of diabetic retinopathy, active urine sediment, rapidly declining kidney function, and diabetes less than ten years (11). A meta-analysis that included 48 studies evaluating KB results in diabetic patients showed a wide range of prevalence of DN (6.5-94%) versus NDRD (3-82.9%) and mixed (4 -45.5%) in their analysis.  The most frequent histopathological findings are Focal Segmental Glomerulosclerosis (FSGS), IgA Nephropathy (IgAN), and acute tubulointerstitial nephritis (ATIN) (12). Therefore, there is still a lack of consensus on when to perform KB in this population. We aimed to identify the possible clinical and laboratory factors in diabetic patients associated with the occurrence of NDRD in KB. 

Methods

Design and patients

From January 2011 to February 2022, the pathology department of the University of Antioquia at the San Vicente Hospital received a total of 6780 kidney biopsies, of which 201 biopsies were of patients ≥14 years old with native kidneys and diagnosis of diabetes mellitus, that were included in this retrospective cohort study. The indications for KB included acute presentations with persistent renal impairment following acute kidney injury or non-acute presentations with atypical clinical features including (1) sub-nephrotic or nephrotic-range proteinuria or nephrotic syndrome and (2) the presence of microscopic hematuria; or (3) rapid progressive chronic kidney disease.

Data Collection

Data were collected from hospital records and the KB registry at the pathology department; final reports were checked individually. All biopsy reports included the results examined under light microscopy (stained with hematoxylin & eosin, periodic acid-Schiff, Masson’s trichrome, and Jones methenamine silver and with other histochemical stains Congo red if was necessary) and immunofluorescence (for IgA, IgG, IgM, C3, C1q, κ, and λ). Still, only 18.4% had electron microscopy to examine glomerular basement membrane thickness or clarify selected cases. Non-sclerosed and sclerosed glomeruli were counted to ascertain the degree of scarring. Glomeruli with global sclerosis and glomeruli with segmental lesions were quantified as percentages of total glomeruli or viable glomeruli, respectively. IFTA scores were classified according to the estimated rate seen in the cortical area of the biopsy sample as follows: absent (grade 0) as 0%; mild (grade 1) <25>50% of the total area (13). DN was diagnosed and graded according to the Renal Pathology Society classification in two groups: 1) combine grades 1 and 2 described as early DN, and 2) grades 3 and 4 Kimmelstiel-Wilson nodules described as advanced DN. (14)

Clinical variables:  we collected patients’ demographic information (age, sex), prespecified laboratory and clinical variables, duration of diabetes, and retinopathy status at the biopsy. Baseline renal function was recorded using the serum creatinine measurements at least three months before the KB. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration method (CKD-EPI) (15). Retinal status was recorded from clinical records at the last assessment. We also follow the previously available serum creatinine before End-Stage Kidney Disease (ESKD) or death. Our main objectives of interest were a) to identify the possible clinical and laboratory association factors of diabetic patients for the appearance of NDRD in KB; b) To compare patient and ESKD (defined as the need for renal replacement therapy) in patients with diabetic versus nondiabetic renal disease; c) Identify risk factors associated with all-cause mortality in the cohort. Patients were followed from the time of renal biopsy until study endpoints or February 2022. The following clinical definitions were used nephrotic-range proteinuria,24-hour urine protein >3500 mg/d; nephrotic syndrome as defined by the KDIGO guidelines (16), 24-hour urine protein >3500 mg/d plus hypoalbuminemia (less than 3 mg/dl) plus hyperlipidemia and edema; hematuria, >5 red blood cells per high-power field; pyuria, >5 white blood cells per high-power field (17); acute kidney disease according to KDIGO guidelines (18), >0.3 mg/dl baseline serum creatinine in less than three months.

Statistical analysis

Qualitative variables were compared using Fisher's test or chi-square as appropriate. Continuous variables depend on whether they followed a normal distribution with means and standard deviations and those did not differ by median and interquartile range. To compare quantitative variables, Student's t-test was used for variables that followed normality and Wilcoxon's t-test for those that did not follow normality.

A logistic regression analysis was carried out for the primary outcome. The dependent variable was NDRD, and the following variables were entered into the model, conforming to their behavior in the univariate analysis. According to the background in the literature (age, glomerular filtration rate, hematuria, retinopathy, and albuminuria) for this, a stepwise logistic regression model was assessed with the clinical variables of interest, and those that in the univariate analysis had a lower p-value of 0.25. 

For the second aim, we performed a Kaplan-Meier survival curve using as start date, the time of the biopsy until the ESKD or death from all causes or censoring by the last follow up, comparing DN with NDRD by log-rank test. A Cox proportional hazards regression analysis was performed for the third objective and identified possible factors associated with renal survival and patient survival using the time of biopsy as the start date until death from all causes for patient survival or ESKD. The variables in the univariate analysis had a p of less than 0.25. According to the literature for the event's development, clinically relevant ones were entered into the Cox regression model. Finally, several prediction models were proposed in an exploratory manner through various logistic regression analyses. The outcome variable was defined as the final biopsy result of any NDRD or mixed versus DN alone in all cases. The independent variables were initially included according to a previous literature review. The variables were selected by a step-by-step method using a significance level of p < 0>

Figure 1: Sampling methodology for patients with kidney biopsy diagnosed with diabetes mellitus from January 2011 to February 2022 at the Department of Pathology Antioquia at University and San Vicente Hospital.

Results

A total of 201 patients diagnosed with diabetes mellitus older than 14 years underwent KB during the study period from January 2011 to February 2022 (fig 1). The mean ± SD age was 56 ± 13 years, the median diabetes mellitus duration 7 (IQR 3 – 13) years, with glycosylated hemoglobin (HbA1c) 7.2(6,4-9,0), and the median serum creatinine was 2 mg/dl, and retinopathy was present in 33% of the cohort.  The KB reports that 41% of patients had DN, 16% mixed, and 43% NDRD. 84% of the patients had high blood pressure, and 76% received Angiotensin-Converting Enzyme (ACEIs) or Inhibitors Angiotensin II receptor blockers (ARBs). The 3 most common causes leading to biopsy were nephrotic syndrome 36.3% (n=73), proteinuria 30.3% (n=61) and acute kidney injury 18.9% (n=38), table 1.

Histopathological findings 

Of the eighty-three DN alone, 92.7% (n=77) present advanced DN classified as grades 3 and 4 containing Kimmelstiel-Wilson nodules, and only 50.6% had diabetic retinopathy. The most frequent histological finding in the KB from the NDRD patients was focal segmental glomerulosclerosis (FSGS), found in twenty-three patients (26.7%), followed by IgA nephropathy. Mixed (NDRD plus DN) most prevalent was tubulointerstitial nephritis with fourteen (45%) individuals, and just six patients (18.7%) had a glomerulopathy in this subgroup, see table 2.

Characteristics

Total

n = 201

n (%)

Diabetic Nephropathy 

n= 83 (41%)

Diabetic Nephropathy plus other

n = 32 (16%)

Non-diabetic renal disease

n = 86 (43%)

p-Value
Sociodemographic
Sex – Male107 (53%)43 (52%)15 (47%)49 (57%)0.590
Residence – Urban125 (62%)48 (58%)16 (50%)61 (71%)0.063
Clinical  
Age, media (years) mean ± SD56 ± 1352 ± 1256 ± 1161 ± 14<0>
Weight (kg) mean ± SD75 ± 1474 ± 1474 ± 1276 ± 150.629
Systolic blood pressure (mmHg) at the time of kidney biopsy mean ± SD133 ± 16136 ± 17132 ± 12131 ± 160.165
Diastolic blood pressure (mmHg) at the time of kidney biopsy median ± SD76 ± 1077 ± 1077 ± 876 ± 90.526
Medical history
Diabetes mellitus     
Type 116 (8%)11 (13%)1 (3%)4 (5%)0.077
Type 2185 (92%)72 (87%)31 (97%)82 (95%)
DM duration (years) Median (I.Q.R.)7 (3 - 13)10 (5 - 17)8 (3 - 13)5 (2 - 10)<0>
Hypertension168 (84%)71 (86%)29 (91%)68 (79%)0.075*
Obesity70 (35%)26 (31%)12 (38%)32 (37%)0.632
Chronic kidney disease97 (48%)42 (51%)15 (47%)40 (47%)0.823
Dyslipidemia123 (61%)49 (59%)20 (63%)54 (63%)0.895
Alcohol34 (17%)15 (18%)6 (19%)13 (15%)0.791
Smoking65 (32%)19 (23%)12 (38%)34 (40%)0.053
Drug abuse4 (2%)2 (2%)1 (3%)1 (1%)0.661
Biomass smoke exposure16 (8%)-9 (28%)7 (8%)<0>
Retinopathy67 (33%)42 (51%)14 (44%)11 (13%)<0>
ACEIs or ARBs153 (76%)63 (76%)27 (84%)63 (73%)0.244
Verapamil use13 (6%)3 (4%)1 (3%)9 (10%)0.176
Statins use113 (56%)46 (55%)19 (59%)48 (56%)0.837

Diabetes medication

Insulin

Metformin

Insulin + metformin

SGLT2i +/- metformin

Other medication*

 

77(38%)

53(26%)

24(12%)

7(3.5%)

40(20%)

 

43(52%)

11(13%)

10(12%)

1(1.2%)

18(22%)

 

14(44%)

7(22%)

3(9.4%)

1(3.1%)

7(22%)

 

20(23%)

35(42%)

11(13%)

5(5.8%)

15(17%)

 

0.723

0.054

0.145

0.625

0.078

Laboratories
Creatinine (mg/dl)2.0 (1.3 – 3.3)1.9 (1.3 – 3.1)2.4 (1.6 – 3.9)1.9 (1.0 – 3.1)0.157
Glomerular filtration rate (ml/min)32 (17 – 55)34 (21 – 53)29 (13 – 41)33 (17 – 68)0.195
24-hour urine protein (mg/24 h)3347 (1375 – 6185)3985 (2100 – 6627)2419 (800 – 8100)2285 (885 – 5414)0.068
HbA1c (%)7.2 (6.4 – 9.0)7.7 (6.5 – 9.3)7.3 (6.4 – 10.2)6.9 (6.3 – 8.3)0.097
Hemoglobin (g/dl)11 (9 – 13)11 (9 – 12)11 (10 – 12)13 (10 – 14)<0>
Hematocrit (%)33 (28 – 40)31 (27 – 36)32 (27 – 35)36 (29 – 44)<0>
Glycemia (mg/dl)144 (114 – 205)159 (116 – 230)167 (135 – 248)132 (107 – 174)0.013
Total Cholesterol (mg/dl)189 (154 – 255)183 (147 – 233)246 (185 – 273)185 (147 – 254)0.115
LDL Cholesterol (mg/dl)106 (80 – 154)106 (83 – 137)147 (94 – 175)102 (78 – 154)0.282
Albumin (g/dl)3.2 (2.5 – 3.6)3.0 (2.5 – 3.5)3.0 (2.4 – 3.5)3.4 (2.7 – 3.8)0.071
Parathyroid hormone (pg/ml)93 (52 – 164)107 (63 – 164)120 (56 – 196)73 (48 – 144)0.122
Albumin-to-creatinine ratio     
<30>28 (14%)8 (10%)7 (22%)13 (15%)0.054
30-300 (mg/g)52 (26%)16 (19%)7 (22%)29 (34%)
>300 (mg/g)109 (54%)54 (65%)13 (41%)42 (49%)
Unknown12 (6%)5 (6%)5 (16%)2 (2%)
Pyuria52 (26%)17 (20%)12 (38%)23 (27%)0.130
Hematuria62 (31%)22 (27%)10 (31%)30 (35%)0.560

SD, Standard deviation; IQR, interquartile Range; HbA1c, glycosylated hemoglobin; ACEIs, Angiotensin-Converting Enzyme; ARBs, Inhibitors Angiotensin II receptor blockers, SGTL2i sodium-glucose cotransporter 2 inhibitors

 

Table 1: Descriptive analysis of patients diagnosed with diabetes mellitus with a kidney biopsy.

 

Total

n = 118 (%)

Non-Diabetic Renal Disease 

n= 86 (%)

Diabetic Nephropathy plus other

n = 32 (%)

Acute Tubulointerstitial Nephritis30 (25.4)16 (18.6)14 (45)
FSGS24 (20.3)23 (26.7)1 (3.1)
IgA nephropathy13 (11)11 (12.8)2 (6.2)
Membranous nephropathy11 (9.3)9 (10.5)2 (6.2)
ANCAS6 (5.1)6 (7)0
MPGN6 (5.1)5 (5.8)1(3.1)
ATN7 (5.9)3 (3.5)4(12.5)
Chronic Interstitial Nephritis4 (3.4)3 (3.5)1(3.1)
Amyloidosis2 (1.7)2 (2.3)0
Hypertensive nephropathy2 (1.7)2 (2.3)0
 Monoclonal gammopathy3 (2.5)2 (2.3)1(3.1)
Post-infectious glomerulonephritis3 (2.5)2 (2.3)1(3.1)
Thin basement membrane nephropathy1 (0.8)1 (1.16)0
Lupus Nephritis2 (1.7)1 (1.16)1(3.1)
Pyelonephritis3 (2.5)03 (9.4)
C3 nephropathy1 (0.8)01 (3.1)
FSGS, Focal segmental glomerular sclerosis; ANCAS: neutrophil anti-cytoplasmic antibodies glomerulonephritis; MPGN, membranoproliferative glomerulonephritis; ATN, acute tubular necrosis

Table 2. Histopathological findings in patients with non-diabetic renal disease and diabetic nephropathy plus another diagnosis.

Factors associated with non-diabetic kidney disease in kidney biopsy

Two independent predictors were identified in the univariate and multivariate analysis; each year above the mean age (56 years) increases the risk of presenting NDRD (OR, 1.05; 95% CI, 1.02–1.09; p = 0.002) in the KB. The diabetic retinopathy significantly decreases the occurrence of NDRD (OR, 0.23; 95% CI, 0.09–0.60; p = 0.002), see table 3.

 VariableUnivariate analysisMultivariate analysis
 OR CI 95%p-ValueOR CI 95%p-Value
 Age  1.051.02 – 1.08<0>1.051.02 – 1.090.002
 Male0.810.44 – 1.490.5001.000.44 – 2.300.995
 Glomerular filtration rate1.011.00 – 1.020.1971.000.99 – 1.020.750
 Hematuria1.440.74 – 2.790.2821.090.44 – 2.670.852
 DM duration0.920.88 – 0.96<0>0.960.90 – 1.020.157
 Retinopathy0.130.06 – 0.29<0>0.230.09 – 0.600.003
 Albumin1.591.05 – 2.390.0271.600.85 – 3.010.148
 Proteinuria1.000.99 – 1.000.3661.000.99 – 1.000.609

Table 3. Univariate and multivariate logistic regression analysis of diabetic nephropathy versus non-diabetic renal disease. Regression with all continuous quantitative variables (albumin and proteinuria do not show collinearity).

Patient and renal-censored survival diabetes nephropathy versus non-diabetic renal disease 

Fifty-seven (28.3%) patients died during the follow-up, the most common cause was infection (n=30, 52.6%), continued by cardiovascular cause (n=16, 28%). The patient survival with DN rate was 52%, and for NDRD, 60% in the first year, 25% and 28% in the third year, and 12,5% and 15% in the fifth year, respectively, figure 2a.  The renal survival with DN rate was 40% and for NDRD plus mixed 38% in the first year, figure 2b. There was no significant difference between patients and renal survival if they presented DN or NDRD.

Figure 2. (a) Patient survival rates for diabetic nephropathy versus mixed (diabetic nephropathy plus non-diabetic renal disease). (b) Renal survival rates diabetic nephropathy versus mixed (diabetic nephropathy plus non-diabetic renal disease)

Patient and renal-censored survival associated factors.

Univariable and multivariate Cox proportional hazards regression models were performed to estimate the adjusted risk for lower patient and renal survival. Patient survival multivariate analysis showed albumin >3 g/dL increases the survival of overall patients that were biopsied; HR, 0.29 (95% CI, 0.12 – 0.68; p = 0.005), as does having proteinuria of less than 3.5 g/24 hours; HR, 0.37 (95% CI, 0.15 – 0.95; p = 0.030). On the contrary, age over 56 years decreases patient survival, HR, 1.04 (95% CI, 1.01–1.06; p = 0.05). These findings were similar in the subgroup of only type 2 diabetic patients. The difference that in this population, not having hematuria was also related to better survival, HR, 0.37 (95% CI, 0.15 – 0.95; p = 0.030). Multivariate analysis showed a marked association with the decreased renal survival associated with diabetic retinopathy, HR, 3.37 (95% CI, 1.36 – 8.33; p = 0.009).

Model I. Univariable and multivariable Cox analysis of predictors of patient survival in the entire population.
Variable                 Univariate analysis                                                                      Multivariate analysis
HRCI 95%p-ValueHRCI 95%p-Value
Age1.000.98 – 1.020.8151.041.01 – 1.060.05
Sex (Male)0.880.52 – 1.490.6330.560.26 – 1.220.143
eGFR >60 ml/min/1.73 m20.760.39 – 1.480.4230.820.38 – 1.760.607
Hematuria0.830.47 – 1.470.5200.540.23 – 1.240.144
DM duration (< 5>0.780.43 – 1.430.4260.740.33 – 1.650.463
Retinopathy0.890.51 – 1.580.6981.250.60 – 2.620.557
Albumin >3.0 gr/dl0.600.32 – 1.130.1120.290.12 – 0.680.004
Proteinuria <3>1.060.59 – 1.920.8480.370.15 – 0.950.039
Diabetic nephropathy non-diabetic renal disease0.770.45 – 1.320.3460.870.41 – 1.850.718
       
Model II. Univariable and multivariable Cox analysis of predictors of patient survival in the type 2 diabetes mellitus population
Variable                                                                 Univariate analysis                                                     Multivariate analysis   
 HRCI 95%P-ValueHRCI 95%P-Value
Age1.000.98 – 1.020.8841.041.00 – 1.090.044
Sex (Male)0.900.52 – 1.560.6970.550.24 – 1.230.144
eGFR>60 ml/min/1.73 m20.780.40 – 1.520.4600.910.42 – 2.000.819
Hematuria0.810.45 – 1.450.4730.400.16 -0.990.048
DM duration (< 5>0.810.44 – 1.500.51310.850.37 – 1.920.693
Diabetic retinopathy0.870.47 – 1.590.6471.340.62 - 2920.459
Albumin >3.0 gr/dl0.660.34 – 1.260.2040.280.11 – 0.680.005
Proteinuria <3>0.960.52 – 1.780.9010.330.13 – 0.860.024
Diabetic nephropathy non-diabetic renal disease0.760.44 – 1.340.3490.780.35 – 1.780.559
Model III. Univariable and multivariable Cox analysis of predictors renal survival in the entire population.
Variable                                                                Univariate analysis                                                                         Multivariate analysis                                                 
 HRCI 95%p-ValueHRCI 95%p-Value
Age0.980.96 – 1.000.0660.980.95 – 1.010.181
Sex (Male)0.750.42 – 1.330.3270.720.34 – 1.530.395
eGFR >60 ml/min/1.73 m20.990.98 – 1.010.3530.980.96 – 1.000.029
Hematuria0.900.48 – 1.700.75111.020.42 – 2.460.962
DM duration (< 5>1.000.96 – 1.040.9830.960.91 – 1.020.183
Retinopathy2.221.18 – 4.170.0133.371.36 – 8.330.009
Albumin >3.0 gr/dl1.000.73 – 1.380.9990.900.57 – 1.420.648
Proteinuria <3>1.001.00 – 1.000.8061.001.00 – 1.000.132
Diabetic nephropathy, non-diabetic renal disease0.910.51 – 1.650.7681.170.54 – 2.540.697

 

Table 4. Univariable and multivariable Cox analysis for overall patient survival and renal survival.

During the exploration of potential predictive strategies, the model with the clinical variables age, diabetic retinopathy, and time of diabetes offered the best predictive performance. The area under the discrimination curve was 0.75 (95% CI, 0.67-0.81) with an acceptable Hosmer Lemeshow test and calibration plot, figure 3.

Figure 3. Predictive strategies, a model with clinical variables age, diabetic retinopathy, and time of diabetes

Discussion

We present our retrospective cohort study in a reference pathology center of diabetic patients who underwent KB in the last decade. The most frequent indication for KB was proteinuria, whether in the nephrotic range or not. In general, KB was a safe procedure, with just 3.98% minor complications and no death caused by it. 

NDRD in patients with diabetes has a wide range in prevalence (12,19-23); this phenomenon is perhaps due to the lack of consensus on the indications for KB from each center (24). In our cohort, the prevalence of NDRD alone was 43%, like those found in the largest cohorts in Europe and the USA, 49.6% and 35.4%, respectively (25,26). Focal segmental glomerulosclerosis was the most prevalent glomerulopathy within the NDRD alone in our study, followed by ATIN, IgAN, and membranous nephropathy, which differs from previous reports literature, in which IgAN was the main finding (27-34). In a study previously carried out by our group that included the review of glomerular disease in 1040 kidney biopsies in the general population, this same distribution of prevalence was also found, which is a similar tendency in Latin America and black race (35). These results are important because they are pathologies susceptible to other treatments that impact better kidney outcomes (36,37).

In the logistic regression model for the occurrence of NDRD, we identified as associated factors the older age (OR, 1.05; 95% CI, 1.02–1.09; p = 0.002) and the absence of diabetic retinopathy (OR, 0.23; 95% CI, 0.09–0.60; p = 0.002), this data is also support by the meta-analysis published by Liang et al. (38), who reported an inversely proportional relationship between the presence of retinopathy and the diagnosis of NDRD. Many researchers have long considered diabetic retinopathy a clinical characteristic of advanced diabetes that would rule out the need for KB in diabetic patients with renal deterioration signs (39,40). But older age (>56 years) has not been previously described as an associated factor as far as we know from the review carried out by our group.

The Cox analysis showed that a normal albumin level (HR, 0.29; p = 0.004) and sub-nephrotic proteinuria (HR, 0.37; p = 0.030) had better patient survival. The predictive component of proteinuria with the progression of kidney disease and cardiovascular mortality has been widely described as worse renal survival with higher amounts [41]. While advanced age (HR, 1.04; p = 0.05) was established as a factor associated with less survival, older individuals are usually linked to other comorbidities that are also frequent in both diabetic patients and those with chronic kidney disease (42-44), which can contribute to the sum of mortality rates (45,46). To our knowledge, after reviewing the available literature, our study was the first to describe independent factors related to better patient survival in a cohort of diabetic patients with KB. 

On the other hand, patients with an eGFR >60 ml/min had better survival, while the presence of diabetic retinopathy was the only independent factor related to worse renal survival. Tan et al. (47) compared NDRD with ND, finding that renal prognosis was generally better with NDRD without specifying associated aspects. Also, Bermejo et al. (48) identified the presence of DN or NDRD plus DN as factors associated with higher mortality in their cohort. Also, in another study, Bermejo et al. (49) related advanced age, peripheral vascular disease, increased creatinine levels, and DN as risk factors for poor renal survival. 

We analyzed the type 2 DM subgroup again older age was correlated with less patient survival. Likewise, the absence of hematuria stands out as a protective factor in terms of survival (<5>10 erythrocytes/field). This presence of red blood cells of glomerular origin in DN is due to alterations in the glomerular basement membrane or to microaneurysms that can rupture [51-55]

Since no single variable has sufficient concordance with the final histological result, it is impossible to rely on a single parameter to make the final clinical decision to perform a KB. However, there is the possibility of building multivariate models that take advantage of the predictive properties of a set of variables simultaneously and support clinical decision-making [56]. In our study, the model with the variables age, retinopathy, and years with diabetes seems to work as a sensitive strategy to rule out DN alone and more strongly justifies a KB in diabetic patients.

Our study has limitations related to being retrospective. In addition, the subjectivity is related to histopathological studies. On the other hand, there is a selection bias since the biopsies are only from diabetic patients with a high suspicion of NDRD. The presence of proteinuria was one of the indications, so our results could be overestimated the true prevalence of NDRD.

Finally, NDRD is a frequent condition, as demonstrated by this cohort of Mestizo (Latino) patients; in addition, the identification of some characteristics such as the older age of the patient as well as the absence of retinopathy can be helpful when deciding whether to perform a KB because the high correlation to have other findings than DN on the histopathological results.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

img

Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

img

Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

img

Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

img

Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

img

Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

img

Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

img

Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

img

Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

img

Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

img

Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

img

Luiz Sellmann