Cast Nephropathy Research Articles

Time is nephron: Daratumumab plus CyBorD in newly-diagnosed multiple myeloma with cast nephropathy: A report of five cases

Background: Renal failure is a common complication of multiple myeloma, often due to overproduction of light chains. Case presentation: Light chain cast nephropathy in newly-diagnosed multiple myeloma is associated with inferior outcomes. Proteasome inhibitors and immunomodulatory drugs with therapeutic plasma exchange can rapidly reduce light chain levels and confer remission; however, optimal delivery of these agents is limited by decreased renal function, and plasma exchange is often limited to tertiary centers. Conclusion: These cases highlight the utility of daratumumab with cyclophosphamide, bortezomib, and dexamethasone for acute renal failure in newly-diagnosed multiple myeloma and a clinical diagnosis of cast nephropathy.

Lambda light chain - restricted non - crystalline proximal tubulopathy with cast nephropathy in multiple myeloma: a case report and literature review

BackgroundMultiple myeloma (MM) often causes renal tubular damage, such as the light chain cast nephropathy (LCCN) and the light chain proximal tubulopathy (LCPT). The excessive light chains deposited in the proximal and distal tubules usually manifest with different characteristics, leading to a rare coexistence of the two pathological conditions. Here we report a unique case of a patient with multiple myeloma (MM) who presented with acute kidney injury (AKI) due to dual conditions of λ light chain-restricted non-crystalline LCPT and LCCN. This report reviews the clinical presentation and histological findings, comparing them with previously published cases.Case presentationA 49-year-old male patient was admitted with a chief complaint of “fatigue, loss of appetite for 40 days and elevated blood creatinine for 10 days.” In serum and urine, the λ light chain level and the ratio of κ to λ free light chain were 1235 mg/dl and 93.25 mg/dl, 0.0022 and 0.0316, respectively. Additionally, serum protein electrophoresis showed an M-spike with monoclonal IgD-λ. Bone marrow puncture revealed 30.5% primitive naive plasma cells, indicative of IgD-λ MM. Light microscopy of kidney biopsy specimen showed periodic acid-Schiff (PAS)-negative cytoplasm in some proximal tubules and PAS-negative casts with a rigid appearance in some distal tubule lumens. On immunofluorescence, these proximal tubular epithelial cells cytoplasm and casts stained exclusively with λ-light chains. Electron microscopy did not reveal any crystalline inclusions. Given the clinical and bone marrow puncture findings, the overall pathological presentation was LCPT with LCCN secondary to IgD-λ MM. After chemotherapy and dialysis, the patient’s condition was improved and he was tracked in follow-ups.ConclusionIn some tubular renal injuries caused by MM, the morphological changes are subtle and often overlooked. In this paper, we present a rare case of LCPT with LCCN showing λ restriction in patient with MM. Through the clinicopathological analysis of patients, the understanding of the disease can be deepened and the diagnosis rate improved.

Features that characterize monoclonal light chain ("myeloma") cast nephropathy with immunofluorescence challenges and emphasis on electron microscopy.

Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasias. The serum-free light chain assay is used in patients, mostly older, with unexplained acute kidney injury to screen for potential myeloma cast nephropathy. This study consists of a systematic review of diagnostic features in myeloma cast nephropathy. The morphological features of tubular casts in patients with multiple myeloma have not been systematically analyzed. This study focuses on the morphology of these casts, emphasizing ultrastructural features, in a series of 23 patients with light chain ("myeloma") cast nephropathy and compared them with casts in 10 patients with various diseases. The immunofluorescence data were correlated with morphological findings to provide diagnostic assessments and practice guidelines. The ultrastructural features identified as diagnostic of casts associated with myeloma included: amyloid and crystals in the casts, multiple well-defined fracture planes forming a complex jigsaw puzzle arrangement of cast contents, indicative of the fragility of the immunoglobulin light chains involved, and reactive tubular cells lining the tubules with the casts. These features were seen in 95.2% of MCN cases and none of the casts in other renal conditions. Myeloma casts exhibited light chain monoclonality in a significant percentage of the MCN cases and often no staining for IgA or IgM. In contrast, the majority of non-myeloma casts stained for both kappa and lambda light chains, lgA, and lgM, and showed ultrastructurally a rather uniform finely to coarsely granular electron density occasionally admixed with cellular debris.

The Role of Monoclonal Antibodies in the Treatment of Myeloma Kidney Disease.

Renal failure is one of the most important manifestations of multiple myeloma. It is caused by renal lesions such as cast nephropathy, immunoglobulin deposition disease, AL amyloidosis or other glomerular and/or tubular diseases, mostly due to the toxic effect of free light chains in serum. Renal failure can represent a clinical emergency and is associated with poor outcome in newly diagnosed and relapsed/refractory multiple myeloma patients. Although progression-free survival and overall survival have improved with the introduction of novel agents, renal failure remains a challenge for the treatment of patients with multiple myeloma. Monoclonal antibodies are a component of therapy for newly diagnosed and relapsed/refractory patients and, based on clinical trials and real-world experience, are also safe and effective for subjects with renal failure, even if they are on dialysis. Most of the data are on anti-CD38 and anti-SLAM7 antibodies, but new antibody-drug conjugates such as belantamab mafodotin and bispecific antibodies also appear to be effective in myeloma kidney disease. In the future, we will have to face some challenges, such as defining new criteria for renal response to treatment, defining specific trials for these difficult-to-treat patients and integrating different therapeutic options.

A Series of Eight Cases of Pigment Nephropathy: An Obscured Aspect of Acute Kidney Injury.

Pigment-induced acute kidney injury (AKI) is an important and preventable complication of rhabdomyolysis or hemolysis. It is characterized by the release of free heme pigment (myoglobin or hemoglobin) in the circulation, leading to direct injury of the proximal tubuleand distal tubule obstruction by pigment cast. We are reporting eight cases of pigment-induced AKI, including six cases of myoglobin cast nephropathy and two cases of hemoglobin cast nephropathy.The causes of rhabdomyolysis were strenuous exercise, infection/febrile illness, and drug-induced neuroleptic malignant syndrome. Paroxysmal nocturnal hemoglobinuria and anti-tuberculosis treatment (rifampicin and isoniazid) had led to hemoglobin cast nephropathy each in one case. Seven cases had severe renal failure requiring dialysis.Short-term renal outcome was favorable. However, long-term follow-up is necessary to determine whether pigment-induced AKI has delayed sequelae. Therefore, clinicians should consider rhabdomyolysis or hemolysis as potential hidden causes of AKI in diverse clinical conditions, especially those of non-traumatic origin, to achieve an accurate diagnosis.

Outcomes of therapeutic plasma exchange for the treatment of patients with multiple myeloma cast nephropathy.

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p=0.006), and achievement of ≥VGPR (OR 21.7 p<0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p=0.09). With a median follow-up of 36.4months, the median overall survival (OS) was 11months. On multivariable analysis, achievement of renal response (hazard ratio [HR]0.3, p<0.0001) and newly diagnosed disease (NDMM; HR 0.43, p=0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p=0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise.

Outcomes of myeloma cast nephropathy in the era of anti-CD38 monoclonal antibody-based frontline therapy: A retrospective cohort study.

7555 Background: Myeloma cast nephropathy (MCN) has been a well-known negative predictive marker in newly diagnosed multiple myeloma (NDMM). Anti-CD38+ monoclonal antibodies (mAb) have improved outcomes, but little is known about their impact in patients with MCN. We performed a retrospective cohort study to investigate the outcomes of patients with MCN in the era of anti-CD38+ mAb-based frontline therapy. Methods: 115 NDDM patients received frontline anti-CD38+ mAb from 11/15/18 to 1/24/23. MCN was defined as evidence of light chain casts on biopsy, serum creatinine of &gt;2mg/dL, or 2021 CKD-EPI eGFR of &lt;40mL/min/1.73m2; ≥1g/d proteinuria; and involved FLC ≥50mg/dL. 23 had MCN; 92 were contemporary controls. We obtained data regarding clinical course. Results: 6 MCN patients needed hemodialysis (HD) at diagnosis. MCN patients had similar R2-ISS to controls. Median proteinuria in MCN patients was 5.7g/d more than in controls; serum creatinine (Cr) was 3.2mg/dL higher; and median hemoglobin was 1.5g/dL less. More MCN patients received quadruplet regimens (86.9% vs 62.0%, p = 0.010); similar proportions were transplanted. At 1, 3, and 6 months, serum Cr was higher in MCN patients (p &lt; 0.001, p = 0.002, p = 0.002). Urine protein:creatinine ratios trended toward difference at 1 month (2.04 vs 0.15g/g MCN vs controls, p = 0.061) but were similar at 3 and 6 months. Response rates at 6 months did not differ. 4 MCN patients still required HD after 6 months. Median follow-up was 23.0-23.5 months. 4 MCN patients died, 1 due to progressive disease. No significant difference in disease-free survival (DFS; HR = 0.58, 95% CI 0.20-1.64, p = 0.295), time to next treatment (TTNT; HR = 0.53, 95% CI 0.20-1.39, p = 0.191), or overall survival (OS; HR 0.610, 95% CI 0.19-1.98, p = 0.406) was seen at any point between MCN and control cohorts. 1 year DFS, TTNT, and OS were: 87.0% MCN, 94.5% control; 77.2% MCN, 91.7% control; 87.9% MCN, 96.1% control. By statistical equivalence testing, MCN DFS and TTNT were within 6 months of control DFS and TTNT (p = 0.038, p = 0.032); MCN OS was within 5 months of control OS (p = 0.034). Conclusions: Patients with NDMM and MCN who receive upfront anti-CD38+ mAb therapy experience prolonged survival compared to prior findings. Anti-CD38+ mAb may substantially reduce, though not fully eliminate, the negative survival impact of MCN. Multiple mechanisms, including time to proteinuria resolution, may be involved. Further study is warranted. [Table: see text]

Rapid reduction of free light chains and improvement in renal outcomes in patients with newly diagnosed multiple myeloma admitted with acute kidney injury with daratumumab-based therapy and without plasmapheresis.

7525 Background: Cast nephropathy is the most common cause of acute kidney injury (AKI) in patients with multiple myeloma (MM), where light chain accumulation in the distal nephron leads to obstruction and injury of the distal and collecting tubules. A prompt reversal of renal injury is paramount to improve outcomes. Daratumumab (dara), an anti-CD38 monoclonal antibody, has significant clinical efficacy in MM. We report the effects of early initiation of dara-based therapy on sFLC reduction and renal recovery in pts admitted with a new diagnosis of MM and AKI. Methods: Between April 2016 and Dec 2023, pts admitted with newly diagnosed MM (NDMM) with AKI (sCr ≥2 mg/dL and/or eGFR &lt;30 mL/min/1.73 m2 by CKD-EPI) and involved sFLC ≥500 mg/L who started dara-based therapy were identified and retrospectively reviewed. We studied pts who started treatment ≤14 days of presentation. Outcomes included sFLC kinetics and renal outcomes per IMWG criteria at 3 months. Results: We identified 20 NDMM pts. Median age was 65 (range 44-87). Median peak sCr at admission was 6.5 mg/dL (range 3.1-17.8) with median eGFR of 8 mL/min/1.73 m2 (range 2-16). Nine pts started hemodialysis (HD). The median peak sFLC at diagnosis was 6603 mg/L (range 1839-26,023). Initial dara regimens included cyclophosphamide, bortezomib, and dexamethasone in 11 pts (55%) and with bortezomib and dexamethasone in 9 pts (45%). Median time between presentation and dara start was 3 days (range 0-10). No pts underwent plasmapheresis. Within 1 cycle of therapy, all 20 pts achieved sFLC reduction ≥50% at a median of 3 days (95% CI, 3-7 days). Median time to sFLC ≤500 mg/L was 13 days (95% CI, 9-33 days), and this was in 15 out of 16 pts (94%) assessable for response after 1 cycle of treatment. At 3 m, the overall renal response (≥minor response) was 85% (N=17), with complete, partial, and minor responses in 50% (N=10), 10% (N=2), and 25% (N=5), respectively. Twelve pts (60%) recovered renal function with eGFR ≥40 mL/min. Of 9 pts who required HD, 4 and 6 pts were free of HD at 3 m and 12 m, respectively. Two pts on HD died within 3 m (age 86, from aspiration pneumonia; age 87, from progressive disease); and 1 continued on HD at 12 months. Fourteen pts (70%) later added lenalidomide, and 3 pts (15%) underwent autologous stem cell transplant. The IMWG ORR was 100% with VGPR 90%. With a median follow up of 25 m, median PFS was 47 m (95% CI 12-not reached) and 2-year OS was 84% (95% CI 68-100%). Conclusions: This is the largest reported cohort of NDMM pts hospitalized with AKI treated with dara-based induction therapy. Treatment with dara combinations shows rapid and deep reductions in sFLC, improving renal recovery outcomes. These findings highlight the efficacy of early use of dara in pts with MM-induced AKI and provide an approach without plasmapheresis.

Effect of daratumumab on light chain reduction in newly diagnosed multiple myeloma with light chain cast nephropathy.

7554 Background: Light chain cast nephropathy (LCCN) is present in 16-31% of patients (pts) in newly diagnosed multiple myeloma (NDMM). In pts with an involved serum free light chain (iFLC) &gt;150mg/dL and predominant LC proteinuria, the probability of LCCN is high enough for a clinical diagnosis without the need for kidney biopsy. Early mortality is higher in pts with renal impairment (RI) who did not achieve a renal response (RR), and a rapid reduction in iFLC may predict RR. While the use of bortezomib and dexamethasone (Vd) in upfront therapy has led to marked improvements in outcomes, the optimal regimen is unclear. Methods: We included pts with NDMM and RI (creatinine &gt;2 mg/dL or eGFR &lt;40 ml/min/1.73m2) and a diagnosis of LCCN (iFLC &gt;150mg/dL and light chain proteinuria) at a single center from 2005-2023. Pts with &gt;10% albuminuria or a diagnosis of MGRS or amyloidosis were excluded. Primary outcome was FLC response (iFLC &lt;50mg/dL and &gt;90% reduction, FLC-R) at day 30 (d30). Other outcomes included hematologic response (partial response or better) at d30 and RR (minimal response or better) at d90, based on International Myeloma Working Group criteria. Results: We included 51 pts with characteristics depicted in the table. All pts received therapy with Vd, adding cyclophosphamide (VCd) in 26 (51%), daratumumab (dara, DVd) in 13 (25%), both (DVCd) in 6 (12%) and alone in 6 (12%). At d30, 11 pts (58%) in dara-containing regimens (DVd, DVCd) and 10 pts (31%) in non-dara-containing regimens (Vd, VCd) achieved a FLC-R (p=0.08); dara was associated with higher odds of achieving a FLC-R at d30 (OR 2.9, p=0.03) after adjusting for age, stage and eGFR at diagnosis. At d90, pts receiving dara had a higher rate of RR than those who did not (69% vs 58%, p=0.5); dara was associated with higher odds of a RR at d90 (OR 1.6, p=0.5). After adjusting for age, stage and eGFR at diagnosis, achieving a FLC-R at d30 was associated with higher odds of a RR at d90 (OR 8.9, p=0.02). Conclusions: Prompt reduction of iFLC is an important objective during the early treatment of LCCN in order to achieve a RR, and dara increases the odds of achieving a FLC-R. The use of dara led to higher odds of a RR at d90, but not statistically significant. We confirmed that achieving a FLC-R at d30 was associated with achieving a RR at d90. Our results suggest that the role of a dara should be explored in prospective studies for the upfront treatment of LCCN in NDMM. [Table: see text]

#1827 Myeloma cast nephropathy: is high cut-off hemodialysis effective?

Abstract Background and Aims Light-chain cast nephropathy is the result of intra-tubular precipitation of light-chains produced by a multiple myeloma. Treatment often includes high cut-off filters hemodialysis (HCO) with the purpose of purifying these chains until the chemotherapy response is achieved. The main goal of this study is to analyze our experience and determine if there is a correlation between the amount of chain purified and the conservation of renal function. Method We conducted a retrospective study that includes all patients suffering from myeloma cast nephropathy treated with hemodialysis in our hospital between 2008 and 2023. HCO filters were used in all of the cases and the diagnosis was established by clinical criteria. In the early stages of the study, only those patients who required kidney replacement therapy underwent dialysis. However, in recent years some cases which did not meet the renal replacement criteria were included. Results 27 patients received the treatment, 59,3% were male and the average age was 68,7+/-8 years. Even though the average of glomerular filtration rate (GFR) previous to the myeloma was 72,65+/-20ml/min, it should be underlined that 8 of them suffered from 3-4 stage chronic kidney disease. The mean follow-up was 55 months, after which 16 had passed away. 59,3% were kappa gammapathy and 75% of them had bone disease. Chemotherapy schemes were variable (85% included Bortezomib). The average of dialysis sessions was 8+/-3,8. 7 patients continued undergoing conventional hemodialysis during the hospital stay but only one of them remained in chronic dialysis. The average GFR at the beginning was 12,2+/-7ml/min. Despite the improvement of the renal function, when compared to the previous GFR, a statistically significant reduction in both hospital discharge (43,67ml/min) and after 1- and 2-year periods (51,94 and 39,91ml/min) was observed. No differences in renal function between patients who started dialysis prematurely (GFR&amp;gt;10ml/min) and those who did not were noticed. The light-chain reduction ratio in each dialysis was examined; it was remarkably variable (2-87%). In order to establish a connection between the amount of chain purified and the preservation of renal function, we conducted a correlation analysis between the intra-dialysis reduction of chains and the GFR at hospital discharge and after 1-year, but not statistically interrelations were observed (p=0,376 and 0,633 respectively). Lastly, no connection between the intra-dialysis light-chain reduction and the loss of GFR was detected. Conclusion In patients with myeloma cast nephropathy, a higher purification of light-chains in HCO hemodialysis is not associated with a better preservation of renal function.

#2622 Very late renal recovery in patient with light chain cast nephropathy: the prognostic value of renal biopsy

Abstract Background and Aims Renal biopsy is not necessary to assess LCCN (Light Chain Cast Nephropathy) in patients with laboratory features suggestive of the disease. However, it has been shown that the histological picture often correlates with renal outcome. We present the case of a 55-year-old man with no significant previous medical history that was evaluated in the emergency department for a stage 3 AKI (sCr 17.3 mg/dl, eGFR 3 ml/min/1.73 m2). Laboratory tests showed a Lambda Micromolecular Myeloma (K chains 44.6 mg/l, λ 4160 mg/l and K/ λ 0.01); Bence Jones not evaluable due to anuria. Bone marrow plasmacytosis was 70%. Method The patient started chemotherapy with Bortezomib and Dexamethasone and hemodialysis thrice a week with a PMMA hemofilter in order to improve the FLC (Free Light Chain) removal rate. After three months of treatment the patient achieved a complete hematologic response but he didn't reach any renal response. In order to assess a more precise renal prognosis a kidney biopsy was performed. The histopathological exam showed a Cast Nephropathy (&amp;lt; 5 casts/mm2) associated with low grade interstitial fibrosis and tubular atrophy (IFTA +1). After 5 cycles with Bortezomib and Dexamethasone, one year after onset, the patient underwent ASCT (Autologous Stem Cell Transplantation). Results In the following months, a progressive increase in renal function allowed us to perform a gradual reduction of dialysis rate, until discontinuation occurred 16 months after disease onset. To date, three years after onset, complete hematologic and renal remission persists with an eGFR of 20 ml/min/1.73 m2. Conclusion Renal biopsy, performed even several months after disease onset, could play a pivotal role in cases of LCCN with a discordance between hematologic and renal response. A low cast number and low IFTA grade are known to be positive prognostic factors for renal outcome and they can predict a renal recovery that sometimes could be exceptionally late.

Immunoglobulin repertoire sequencing and de novo sequencing – Powerful tools for identifying free light chains from patients with light chain cast nephropathy

In patients with light chain cast nephropathy (LCCN), abundantly produced monoclonal immunoglobulin free light chains (FLCs) play a vital role in pathogenesis. Determining the precise sequences of patient-derived FLCs is therefore highly desirable. Although immunoglobulin repertoire sequencing (5′ RACE-seq) has been proven to be sensitive enough to provide full-length V(D)J region (variable, diversity and joining genes) of FLCs using bone marrow samples, an invasive and bone marrow independent method is still in demand. Here a de novo sequencing workflow based on the bottom-up proteomics for patient-derived FLCs was established. PEAKS software was used for the de novo sequencing of peptides that were further assembled into full-length FLC sequences. This de novo protein sequencing method can obtain the full-length amino acid sequences of FLCs, and had been shown to be as reliable as 5′ RACE-seq. The two LCCN sequences derived from above the two methods were identical, and they possessed more hydrophobic or nonpolar amino acids compared with the corresponding germline, which may be associated with the pathogenesis.

The Urine Light Chain/eGFR Quotient as a Tool to Rule out Cast Nephropathy in Myeloma-Associated Kidney Failure.

Kidney involvement with resulting kidney failure leads to increased mortality in patients with multiple myeloma (MM). Cast nephropathy (CN), in particular, if left untreated, quickly leads to kidney failure requiring dialysis and has a very poor prognosis for the affected patient. The gold standard for diagnosing kidney involvement is a kidney biopsy. However, due to bleeding risk, this cannot be done in every patient. We recently reported that a quotient of urine light chain (LCurine) to glomerular filtration rate (eGFR) is a non-invasive diagnostic tool for patients with kidney involvement in MM. But this quotient has not yet been tested in everyday clinical practice. In this study, our LCurine/eGFR ratio was tested on 67 patients in two centers. Enrollment took place between January 2019 and September 2023. A total of 18 of the 67 patients had CN. With the threshold defined in our initial paper, we were able to show a sensitivity of 100% with a specificity of 85.7% for CN in patients with MM. As a result, the LCurine/eGFR quotient recognizes 100% of all CN and can therefore detect this group, which has a very poor prognosis, without the need for a kidney biopsy.

Monoclonal immunoglobulin crystalline nephropathies

Monoclonal immunoglobulin (MIg) crystalline nephropathies are rare lesions resulting from precipitation of MIgs in the kidney as crystalline inclusions. They can be categorized into lesions with predominant intracellular crystals (light chain [LC] proximal tubulopathy, LC crystal-storing histiocytosis, LC crystalline podocytopathy] and lesions with predominant extracellular crystals (crystalglobulin-induced nephropathy, crystalline variant of LC cast nephropathy). The majority of these lesions are associated with low tumor burden lymphoproliferative disorders, with the exception of crystalline variant of LC cast nephropathy. Extra-renal involvement (eg, skin, cornea) is frequent. Kidney biopsy is the cornerstone for diagnosis, which often requires electron microscopy and antigen retrieval. A thorough hematologic workup and evaluation of extra-renal involvement is mandatory for management. Treatment of these lesions is with clone-directed therapy, with the goal of achieving hematologic very good partial response or complete response which preserve or improve kidney function. In vitro and in vivo studies, animal models, and novel sequencing techniques have been invaluable tools to understand the pathogenesis of LC proximal tubulopathy, and can be utilized to increase our limited knowledge of the pathogenesis of the other MIg crystalline nephropathies. This review will provide an update on the pathology, renal and hematologic characteristics, extra-renal manifestations, prognosis, treatment, and pathogenesis of MIg crystalline nephropathies.

192 Acute Kidney Injury Due to Acetaminophen Toxicity-Associated Cast Nephropathy

192 Acute Kidney Injury Due to Acetaminophen Toxicity-Associated Cast Nephropathy

Kidney involvement in Wilson's disease: a review of the literature.

Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.

Renal outcome in multiple myeloma patients with cast nephropathy: a retrospective analysis of potential predictive values on clinical and renal outcome

ABSTRACT Objective Cast nephropathy (CN) is the leading cause of acute kidney injury (AKI) in multiple myeloma (MM). Since it is sparsely documented why some patients with CN do achieve a renal response while others do not, we describe a single-center cohort of patients with multiple myeloma and biopsy-confirmed CN to evaluate potential markers of renal response. Methods The data was collected as a retrospective, single-center analysis of CN-patients treated at the Medical University Vienna between 01/01/2004 and 01/01/2022. Baseline parameters and clinical outcome was compared between renal responders and non-responders. Results Among 28 patients with CN, n = 23 were assessed for renal response (14 responders; 9 non-responders). Renal responders were younger (median age: 61 years; 77 years, p = 0.039), showed higher overall survival (153months; 58months, p = 0.044) and achieved hematologic response (≥PR) to first-line therapy (p = 0.029), and complete hematologic response (CR) at any time (p = 0.025) significantly more often. Further, we could show that rapid initiation of anti-myeloma therapy after initial presentation correlated significantly with renal response (median 9 days; 27 days, p = 0.016). Analyses of kidney biopsy specimens revealed that patients with a high IF/TA score showed end stage renal disease (dialysis ≥ 3 months) significantly more often (p = <0.001). Discussion In summary, our data suggests, that a rapid start with systemic hematologic treatment in patients with MM and CN is crucial and achieving an early hematologic response is important for renal recovery. Moreover, achieving a deep hematologic response and subsequent renal recovery improves clinical outcome as reflected by an overall survival benefit.

A Retrospective Cross-sectional Analysis of Renal Complications in Association with Cancer: Insights from 120 Autopsies

Introduction: Kidney diseases frequently complicate cancer and its treatment, contributing to both morbidity and mortality. Malignancies can give rise to various kidney issues, such as glomerulonephritis and Chronic Kidney Disease (CKD). This association operates bidirectionally, with patients experiencing the development of renal diseases due to cancer, and CKD predisposing to cancer. Furthermore, nephrotoxicity induced by chemotherapy can result in Acute Tubular Injury (ATI) and necrosis, imposing limitations on its application. Aim: To evaluate the spectrum of renal pathology in autopsies of malignancies. Materials and Methods: This was a retrospective crosssectional study of complete autopsies of all cases of malignancies performed in the Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. The study was carried out over a 5-year period from January 2015 to December 2019. Analysis of cases with respect to demographics, type of primary malignancy, gross and microscopic features, and the final cause of death was conducted. These findings were meticulously tabulated, with frequencies and percentages calculated for each category. Results: A total of 4392 autopsies were conducted throughout the study period, with 120 of them revealing the presence of malignancies. A total of 38 (31.6%) malignancies were diagnosed for the first time at autopsy. The commonest renal findings on gross were scars (superficial and deep) seen in 40 (33.33%), followed by cortical cysts in 25 (20.83%), granular contracted kidney in 15 (12.50%), mass lesions in 7 (5.83%), abscesses in 7 (5.83%), and swollen, oedematous kidneys in 6 (5%) autopsies. The most frequent renal pathology on microscopy were infective lesions seen in 43 (35.83%), Acute Tubular Necrosis (ATN) in 32 (26.66%), ATI in 30 (25%), followed by malignancies- primary and secondary in 11 (9.16%), tubular casts in 6 (5%), etc. Rare findings included membranous glomerulonephritis and Tumour Lysis Syndrome (TLS) (Acute urate nephropathy) in 1 (0.83%) each. The TLS case had classic histomorphological features of TLS, apart from laboratory parameters. Extensive deposits of uric acid crystals were seen obstructing the tubules as well as some of the glomeruli on microscopy. Conclusion: In one-third of the cases, the malignancy was exclusively discovered during the autopsy. The study revealed a diverse array of lesions, encompassing pyelonephritis, ATN, primary and metastatic renal tumours, cast nephropathy, membranous glomerulonephritis, and TLS. One-fifth of the cases had end-stage renal disease (advanced renal disease). A significant number of the cases exhibited tumour masses within the kidneys. One-fifth of the cases had renal pathology contributing to the final cause of death, further highlighting the association between malignancies and renal pathology

Autoimmune hemolytic anemia in case of myeloma cast nephropathy in tertiary care hospital of Jaipur Rajasthan

Autoimmune hemolytic anemia in case of myeloma cast nephropathy in tertiary care hospital of Jaipur Rajasthan

A Case Series of Bile Cast Nephropathy-induced Rapidly Progressive Renal Failure

Abstract A 45-year-old male presented to the hospital with symptoms of left inguinal swelling, which showed granulomatous adenitis on fine-needle aspiration cytology. He was diagnosed with tuberculous adenitis, for which he was started on antitubercular treatment. After 15 days of antitubercular treatment, the patient developed deranged renal parameters, with serum creatinine of 8.8 mg/dL while serum bilirubin rose to 7.4 mg/dL. The patient was oliguric and underwent four sessions of hemodialysis. Following this, a renal biopsy was done, which showed normal glomeruli with tubular casts that were pigmented, consistent with acute tubular injury secondary to bile cast nephropathy. The patient’s condition improved with one more session of hemodialysis and conservative management. Serum creatinine declined to 1.2 mg/dL, at the time of discharge, with normal urine output. This case illustrates features of bile cast nephropathy presenting as rapidly progressive renal failure secondary to antitubercular treatment.