AUCTORES
Globalize your Research
case presentation | DOI: https://doi.org/10.31579/2690-8808/105
Endocrinology Division, Department of Medicine, Olive View-UCLA Medical Center, David-Geffen School of Medicine, CA, USA
*Corresponding Author: Nasser Mikhail, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
Citation: Nasser Mikhail, (2022) Alendronate-induced nephropathy J. Clinical Case Reports and Studies 3(3); DOI: 10.31579/2690-8808/105
Copyright: © 2022 Nasser Mikhail, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 17 January 2022 | Accepted: 22 January 2022 | Published: 05 February 2022
Keywords: alendronate; nephrotoxicity; bisphosphonates; safety
Background: Alendronate is considered a safe drug with respect to kidney function when used per manufacturer recommendations.
Objective: To describe reported cases of nephrotoxicity associated with alendronate.
Methods: Pubmed search of English literature up to January 14, 2022. Search terms include alendronate, bisphosphonates, proteinuria, renal failure, adverse effects. Pertinent case reports, reviews, and guidelines of professional organizations are included.
Results: Review of literature revealed 7 patients who developed nephrotoxicity likely due to alendronate therapy for osteoporosis. In 5 patients, kidney function was normal before starting alendronate. Five patients presented with nephrotic syndrome and had focal segmental glomerulosclerosis (FSGS) on renal biopsy. Collapsing FSGS was specifically demonstrated in 2 patients. Nephrotoxicity was diagnosed as early as 2 weeks and up to 3 years after starting alendronate. No clear predisposing factors or patient demographic characteristics could be outlined in association with this adverse effect. In addition to discontinuation of alendronate, treatment consisted of glucocorticoids followed by angiotensin-converting enzyme inhibitors and diuretics. In 4 of the 7 patients, renal function did not return to normal and 3 subjects required hemodialysis.
Conclusions: Physicians should be aware that alendronate may be uncommonly associated with nephrotoxicity. Checking protein in urine 2 weeks after starting alendronate and periodically thereafter may help early diagnosis of this serious adverse effect.
Alendronate is an oral bisphosphonate widely used worldwide for prevention and treatment of osteoporosis [1]. Following a single intravenous dose of alendronate, approximately 50% of the drug is excreted in urine [2]. The manufacturer does not recommend the use of alendronate in subjects with creatinine clearance <35 n=5,046),>
However, there are few reports in the literature showing that alendronate may be associated with FSGS, specifically the collapsing variant of FSGF. The latter is an aggressive form of FSGS characterized by severe nephrotic syndrome that rapidly progresses to acute renal failure [4, 5]. Collapsing FSGS was previously reported as uncommon adverse effects of intravenous bisphosphonates, namely pamidronate and zoledronic acid [6, 7]. The main purpose of this article is to describe the characteristics of previously reported cases of alendronate-induced nephrotoxicity, and to draw attention of physicians to this uncommon but serious adverse effect.
Review of literature unraveled 7 patients who presented with nephrotoxicity in association with alendronate therapy for osteoporosis between 1997 and 2015 [8-14] (table1). The age range was 36-79 years. Among the 7 cases reported, 4 were women. One patient had already a diagnosis of FSGS before starting alendronate [11], and another patient had pre-existing chronic kidney disease [10]. Meanwhile, except for osteoporosis, two patients: a 36-year-old man and 55 year-year old woman, had no co-morbidities [12, 13] (table 1). Inspection of table 1 shows that it is difficult to find specific predisposing factors for alendronate-induced nephrotoxicity. In fact, it seems that any age, gender, or race, might be predisposed irrespective of co-morbid conditions (table 1).
Abbreviations: *CKD: chronic kidney disease, **FSGS: focal segmental glomerulosclerosisIt should be emphasized that the first patient with multiple myeloma reported by Zazgornick et al [8] had vomiting 2 weeks after starting alendronate.Thus, dehydration secondary to vomiting might be a precipitating factor for acute renal failure in this patient.
In 2 patients reported as brief “letters to the Editor”, physical exam findings were not reported [8,12]. In the patient described by de la Vega et al [9] who presented with laboratory abnormalities of acute renal failure, physical exam was unremarkable except for basal crackles on lung auscultation. Meanwhile, all remaining cases presented with generalized anasarca due to severe nephrotic syndrome (generalized edema, gross proteinuria, hypoalbuminemia, hyperlipidemia) [10,11,13, 14].
Six of the 7 patients underwent renal biopsy [9-14]. The renal pathology of the case reported by de la Vega et al [9] was described as acute granulomatous interstitial nephritis. In the 5 remaining patients, kidney biopsy findings were consistent with FSGS including 2 cases being specified as collapsing FSGS (table 1) [10,14]. The hallmark pathological feature of collapsing FSGS is marked wrinkling and “collapse” of the glomerular basement membranes associated with hypertrophy and hyperplasia of overlying podocytes [6].
In all patients, alendronate was suspected as the culprit for acute renal injury and was discontinued. Treatment consisted of glucocorticoids for 6-16 weeks in 4 patients [9, 11, 12, 14] (table 1), angiotensin-converting enzyme inhibitors in 2 patients [10,12], and only diuretics in one patient [13]. Regarding the outcome, only 2 patients fully recovered, with disappearance of proteinuria after 40 days [11, 13]. In another patient, kidney function recovered after unknown duration following 3 pulse doses of chemotherapy given for her multiple myeloma [8]. This chemotherapy consisted of dexamethasone, vincristine, and doxorubicin [8]. However, the 4 remaining patients had either partial recovery [9,12] or worsening of kidney function [10]. Moreover, 3 patients progressed to end-stage renal disease that required either transient or permanent hemodialysis [9, 11,14].
The mechanisms of alendronate induced nephrotoxicity are unclear. It is possible that alendronate causes toxic effect in podocytes. The latter represent an important barrier to protein loss in the renal glomeruli, and injury of podocytes results in marked proteinuria [15]. Indeed, podocyte injury was the mechanism by which pamidronate induced its nephrotoxic effects [6]. Garimella et al [14] hypothesized that alendronate might cause injury of podocytes in kidneys similar to its toxic effects on osteoclasts in bones because of similar cytoskeletal structure between podocytes and osteoclasts. This hypothesis is interesting and requires further investigation.
Seven cases of alendronate-induced nephrotoxicity were described. This number is likely under-reported given the widespread use of alendronate. Nephrotoxicity may occur shortly (as early as 2 weeks) or years after alendronate use. Men and women of any age are equally affected. No clear predisposing factors could be identified for such toxic renal effect. Unfortunately, in most cases, nephrotoxicity can lead to acute renal failure which may not be fully reversible. Physicians should be aware of this uncommon but serious adverse effect of alendronate. Since proteinuria is an early sign of alendronate-associated nephrotoxicity, it may prudent to check urine protein 2 weeks after starting alendronate and then periodically every 6 months.
The authors have no conflict of interest to declare.
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.
