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1.
Hematol Oncol ; 42(4): e3293, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38872511

ABSTRACT

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 3 months 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 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months 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 36.4 months, the median overall survival (OS) was 11 months. 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.


Subject(s)
Multiple Myeloma , Plasma Exchange , Humans , Multiple Myeloma/therapy , Multiple Myeloma/mortality , Male , Female , Plasma Exchange/methods , Middle Aged , Aged , Retrospective Studies , Treatment Outcome , Adult , Aged, 80 and over , Kidney Diseases/therapy , Kidney Diseases/etiology
2.
S Afr J Infect Dis ; 39(1): 637, 2024.
Article in English | MEDLINE | ID: mdl-38841341

ABSTRACT

HIV patients frequently develop acute kidney injury (AKI) because of sepsis and diarrhoeal disease. Here, we report a case of an HIV-positive man with partially treated sinonasal plasmablastic lymphoma (PBL) and unexplained AKI. A kidney biopsy revealed two pathological processes. Contribution: While urinary tract obstruction is the most common mechanism by which PBL causes AKI, maintaining a high level of suspicion for multiple pathological processes in cases involving light chain producing PBL.

3.
Biomedicines ; 12(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38790994

ABSTRACT

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.

4.
Nephrology (Carlton) ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38741555

ABSTRACT

This case report describes a rare and interesting case of a patient with multiple myeloma complicated with light chain (LC) cast nephropathy and focal amyloidosis. The patient presented with acute kidney injury, anaemia and bone lesions. The diagnosis was confirmed by bone marrow biopsy, serum and urine electrophoresis and kidney biopsy. The patient was treated with isazomil, pomalidomide and dexamethasone combination chemotherapy, followed by autologous stem cell transplantation. The patient achieved clinical remission, stable renal function and improved serum lambda free LC levels. This case highlights the challenges and advances in the diagnosis and treatment of this condition.

5.
Adv Kidney Dis Health ; 31(2): 111-126, 2024 03.
Article in English | MEDLINE | ID: mdl-38649215

ABSTRACT

The concept of structural kidney damage and renal dysfunction as a result of jaundice attracted attention in the medical community in the early and mid-20th century. The postulated doctrine of the time was that the excretion of elevated concentrations of bile results in bile-stained casts occupying collecting and distal convoluted tubules, degeneration of tubular epithelium, and decreased renal function. Compared to the hepatorenal syndrome, the poster child of hepatology and nephrology collaboration, the notion of structural kidney damage and renal dysfunction as a result of cholemia lost its traction and has almost disappeared from modern textbooks. Today, cholemic nephropathy is experiencing a renaissance, with multiple case reports and case series of jaundiced patients with kidney dysfunction and evidence of bile acid casts upon histologic examination. Published cases include acute hepatitis, chronic liver injury, cirrhosis, and obstructive etiologies. Diagnosis of cholemic nephropathy is based on histological examination, typically showing intraluminal bile casts predominantly located in the distal tubules. In common bile duct-ligated mice, the histomorphological and functional alterations of cholemic nephropathy mimic those seen in humans. Some argue against the concept of cholemic nephropathy and postulate that bile casts are a secondary phenomenon. What we need are carefully designed trials to establish diagnostic criteria and subsequently translate this knowledge into evidence-based therapies.


Subject(s)
Acute Kidney Injury , Cholestasis , Liver Cirrhosis , Humans , Acute Kidney Injury/pathology , Acute Kidney Injury/etiology , Cholestasis/pathology , Cholestasis/complications , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Animals , Bile Acids and Salts/metabolism
6.
Ann Hematol ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558184

ABSTRACT

Therapeutic plasma exchange (TPE) is an extracorporeal technique where patient's plasma containing pathogenic substances is separated and removed from the whole blood, while the cellular component is returned to the patient mixed with replacement solution via an apheresis machine. Due to its ability to remove pathogenic substances from plasma including immunoglobulins, TPE has proven efficacious in the management of various disorders across different medical disciplines, including plasma cell dyscrasias, which are characterized by the abundant secretion of non-functional immunoglobulins produced by an abnormally proliferating plasma cell clone. This review summarizes the current indications of TPE in plasma cell-related disorders and discusses its application, safety, and therapeutic effects.

7.
Int J Hematol Oncol Stem Cell Res ; 18(1): 64-74, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38680711

ABSTRACT

Background: To assess the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal failure. Materials and Methods: A retrospective single-center study included 64 patients (30 men, 34 women) with MM and kidney damage at the onset of the disease, aged 19 to 65 years (median 54), who underwent auto-HSCT from 2013 to 2019. 23 patients (36%) were dialysis-dependent at the time of diagnosis. The analysis was carried out in two groups: the "HD-" group (patients who were independent of hemodialysis during auto-HSCT, n = 54), and the "HD +" group (patients who underwent auto-HSCT while treated with programmed hemodialysis, n = 10). Research results were statistically processed using the Statistica software (version 10.0); the data obtained were presented graphically. Statistical analysis was performed using survival analysis (using the Kaplan-Meier method, with a Log-Rank Test) and frequency analysis (using contingency tables and Fisher's test). Results: The patients dependent on hemodialysis were significantly more likely to require red blood cell transfusions compared to the dialysis-independent patients (100% versus 35%, p = 0.0001). Reactivation of a herpes viral infection and reversible toxic encephalopathy developed significantly more often in the patients from the "HD +" group compared with the patients from the "HD-" group (30% versus 6%, p = 0.04 and 20% versus 0%, p = 0.02, respectively). As a result of the treatment (induction + auto-HSCT), 14 patients (61%) became hemodialysis-independent. There was no transplant-related mortality. With a median follow-up of 48 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 70% and 42%, respectively. Conclusion: Auto-HSCT is a safe and effective treatment for patients with MM complicated by acute kidney injury. Fourteen of 23 (61%) patients became dialysis-independent.

8.
Hematology ; 29(1): 2311600, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38329272

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.


Subject(s)
Acute Kidney Injury , Multiple Myeloma , Humans , Middle Aged , Multiple Myeloma/drug therapy , Retrospective Studies , Kidney , Renal Dialysis/adverse effects , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy
9.
Am J Transplant ; 24(1): 141-144, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37633448

ABSTRACT

Here we discuss the successful utilization of a pair of deceased donor kidneys with bile-cast nephropathy. The donor had a kidney donor profile index of 48% and an acute kidney injury requiring continuous renal replacement therapy. Peak donor bilirubin was 40.5 mg/dL, and renal wedge biopsies showed bile-cast nephropathy. Both recipients had delayed graft function lasting up to 4 weeks. The 4-month biopsies showed mild interstitial fibrosis, tubular atrophy, and a resolution of bile casts. These kidney allografts showed the reversible course of cholemic nephropathy and the potential for increasing the utilization of previously discarded kidneys.


Subject(s)
Acute Kidney Injury , Kidney Transplantation , Humans , Bile , Kidney/pathology , Kidney Transplantation/adverse effects , Acute Kidney Injury/etiology , Transplantation, Homologous , Tissue Donors , Biopsy , Graft Survival
10.
J Hepatol ; 80(2): 268-281, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37939855

ABSTRACT

BACKGROUND & AIMS: Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there is no specific treatment. We revisited its pathophysiology with the aim of identifying novel therapeutic strategies. METHODS: Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI mass spectrometry imaging and liquid chromatography-tandem mass spectrometry. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed in kidney biopsies from patients with CN, mice with a humanized bile acid (BA) spectrum, and via analysis of serum BAs and KIM-1 (kidney injury molecule 1) in patients with liver disease and hyperbilirubinemia. RESULTS: Proximal tubular epithelial cells (TECs) reabsorbed and enriched BAs, leading to oxidative stress and death of proximal TECs, casts in distal tubules and collecting ducts, peritubular capillary leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TECs and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In patients with advanced liver disease, serum BAs were the main determinant of KIM-1 levels. ASBT expression in TECs was preserved in biopsies from patients with CN, further highlighting the translational potential of targeting ASBT to treat CN. CONCLUSIONS: BA enrichment in proximal TECs followed by oxidative stress and cell death is a key early event in CN. Inhibiting renal ASBT and consequently BA enrichment in TECs prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS: Cholemic nephropathy (CN) is a severe complication of cholestasis and an unmet clinical need. We demonstrate that CN is triggered by the renal accumulation of bile acids (BAs) that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells of the kidney take up BAs via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in tubular epithelial cells, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for patients with CN.


Subject(s)
Carrier Proteins , Cholestasis , Kidney Diseases , Liver Diseases , Membrane Glycoproteins , Organic Anion Transporters, Sodium-Dependent , Symporters , Humans , Mice , Animals , Cholestasis/complications , Cholestasis/metabolism , Kidney/metabolism , Symporters/metabolism , Bile Acids and Salts/metabolism , Liver/metabolism , Bile Ducts/metabolism , Liver Diseases/metabolism , Sodium
11.
G Ital Nefrol ; 40(Suppl 81)2023 Oct 03.
Article in Italian | MEDLINE | ID: mdl-38007838

ABSTRACT

Myeloma cast nephropathy is the most common cause of acute kidney injury in patients affected by multiple myeloma. The mainstay of management of cast nephropathy is the clone-based therapy by reducing production and thereby precipitation of light chains. Adjuvant therapy consists of inducing high urine volume flow and alkalinisation, where possible. Extracorporeal removal of light chains is still debated and the advantages of these procedures are not established. The use of safe and low expensive membranes may encourage their use and address their utility.


Subject(s)
Acute Kidney Injury , Multiple Myeloma , Humans , Immunoglobulin Light Chains , Renal Dialysis/adverse effects , Treatment Outcome , Multiple Myeloma/complications , Multiple Myeloma/therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy
12.
Intern Med ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37926541

ABSTRACT

The most common cause of acute kidney injury (AKI) in multiple myeloma is light-chain cast nephropathy (LCCN), which consists of a light chain and Tamm-Horsfall protein (THP). We herein report a 46-year-old woman with hypercalcemia and AKI. A renal biopsy showed crystalline casts, which were consistent with lambda light chains but not THP. Hydration therapy and treatment to lower her serum calcium concentration were initiated immediately. She subsequently received bortezomib-based anti-myeloma therapy and recovered successfully. This was a rare case of LCCN, suggesting that hypercalcemia may play a role in the development of crystalline LCCN.

13.
Turk J Pediatr ; 65(5): 874-880, 2023.
Article in English | MEDLINE | ID: mdl-37853979

ABSTRACT

BACKGROUND: Intravascular hemolysis is a serious and rare condition in children and causes the release of hemoglobin and heme into circulation, which have proinflammatory properties. These substances lead to inflammation, oxidative stress, apoptosis, and organelle dysfunction that lead to acute kidney injury (AKI). We report a pediatric case diagnosed with hemolysis-associated hemoglobin cast nephropathy due to autoimmune hemolytic anemia. CASE: A 4-year-old boy, who was admitted to another hospital with complaints of fever and dark urine for one day, developed anemia and kidney failure in the follow-up, was referred to our hospital. In physical examination, pallor and icterus on the sclera were noted. The patient had low hemoglobin and haptoglobin levels concomitant with high levels of serum lactate dehydrogenase, urea and creatinine. A peripheral blood smear showed marked spherocytes without schistocytes. A kidney biopsy was performed due to ongoing overt hemolysis and dialysis requirement, which showed findings consistent with hemoglobin cast nephropathy. Although the initial polyspecific direct antiglobulin test (DAT) was negative, due to persistent intravascular hemolysis DAT was studied monospecifically and showed IgM antibody positivity. Therefore, a diagnosis of autoimmune hemolytic anemia was made, and corticosteroid treatment was started. Hemolysis immediately ceased and the need for erythrocyte transfusion and dialysis disappeared. CONCLUSIONS: Acute kidney injury associated with hemoglobin cast nephropathy is an extremely rare condition in childhood. Although the initial course is severe and potentially life-threatening, the prognosis is favorable with the treatment of the underlying cause and management of AKI. Therefore, pediatricians should be aware of this rare clinical entity during clinical practice.


Subject(s)
Acute Kidney Injury , Anemia, Hemolytic, Autoimmune , Anemia, Sickle Cell , Male , Humans , Child , Child, Preschool , Hemolysis , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/drug therapy , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Hemoglobins/therapeutic use
14.
Front Nephrol ; 3: 1256672, 2023.
Article in English | MEDLINE | ID: mdl-37885924

ABSTRACT

Background: Bile cast nephropathy (BCN) is an underdiagnosed renal complication associated with severe hyperbilirubinemia and is seen in patients with liver failure who have cholestatic complications. BCN-induced acute kidney injury (AKI) can require hemodialysis (HD), and the molecular adsorbent recirculating system (MARS) is a potentially useful therapeutic option. Case summary: A 57-year-old male presented with jaundice persisting for 1 month, with laboratory test results indicative of hyperbilirubinemia and AKI. Abdominal imaging and a biopsy confirmed biliary ductal dilation secondary to a pancreatic head mass. The patient had rapidly progressive renal failure and refractory hyperbilirubinemia, despite biliary decompression, and was started on HD. Subsequent therapy with albumin dialysis therapy using MARS was successful in reversing the AKI, the cessation of HD, and the restoration of native renal function. Conclusion: In the setting of BCN-induced AKI, timely initiation of MARS can provide a useful therapeutic strategy to reverse renal dysfunction and facilitate intrinsic renal recovery.

15.
Medicina (Kaunas) ; 59(7)2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37512137

ABSTRACT

Background and Objectives: The clinical presentation and survival factors in patients with myeloma-related kidney impairment (MRKI) at diagnosis remain a topic of ongoing research, given the complex interplay between nephrology and hematology. To date, no studies have specifically reported outcomes for these patients in Eastern Europe. Materials and Methods: We conducted a retrospective, unicentric study of consecutive newly diagnosed patients with MRKI in our tertiary nephrology service in Romania between 2015 and 2020; follow-up extended until 1 September 2022, covering a study period of 90 months. Results: We identified 89 consecutive patients with MRKI (median age 66 years, 38% male, median eGFR 5 mL/min). The majority of patients had arterial hypertension (71%) and systemic atherosclerosis (58%), and the most frequent clinical features at presentation were asthenia (75%) and bone pain (51%). Light-chain-restricted myeloma was the most common type (55%), with kappa free light chain being more frequent (53%). Among the patients, 81% presented with acute kidney injury (AKI), and 38% required hemodialysis at diagnosis. During the study period, 65% of the patients died, and hypoalbuminemia and the need for hemodialysis at diagnosis were significantly associated with mortality in multivariate analysis. Conclusions: Patients with MRKI who present to the nephrologist more frequently exhibit light chain restriction and most often present with AKI, with one-third requiring hemodialysis at diagnosis. Moreover, hypoalbuminemia and the initiation of hemodialysis at diagnosis were significantly associated with increased mortality.


Subject(s)
Acute Kidney Injury , Hypoalbuminemia , Multiple Myeloma , Nephrology , Humans , Male , Aged , Female , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Retrospective Studies , Hypoalbuminemia/complications , Acute Kidney Injury/complications , Immunoglobulin kappa-Chains , Kidney
16.
ACG Case Rep J ; 10(7): e01105, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37501938

ABSTRACT

Selective androgen receptor modulators (SARMs) are novel nonsteroidal agents abused for performance enhancement such as anabolic steroids. We report a case of a 27-year-old man who used 3 different SARMs and presented with progressive weakness. Initial laboratory testing showed kidney and liver injury with creatinine 4.8 mg/dL and total bilirubin 43.3 mg/dL. An extensive workup was negative for other causes, and the results of liver and kidney biopsies were consistent with bile cast nephropathy because of SARM-associated drug-induced liver injury. His organ functions improved with the cessation of SARMs and plasmapheresis. Providers need to recognize the extreme consequences of SARM use.

17.
Nephrology (Carlton) ; 28(10): 561-566, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37329237

ABSTRACT

Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma-associated acute kidney injury (M-AKI) in the contemporary era of anti-plasma cell therapy. Patients who received anti-myeloma therapy with M-AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records. Diagnosis of MCN was either biopsy confirmed (BC) or clinically suspected (CS), the latter defined as acute kidney injury with reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and involved serum free light chains (iSFLC) >500 mg/L at diagnosis. Twenty-six patients with M-AKI were identified (BC: n = 13, CS: n = 13). Median eGFR at diagnosis was 12 (interquartile range 6-20) mL/min/1.73 m2 . All six dialysis-requiring patients achieved dialysis independence after 71 (43-208) days. The best-achieved eGFR was 47 (32-67) mL/min/1.73 m2 after 120 (63-167) days post-treatment, which was maintained at 47 (33-66) mL/min/1.73 m2 12 months post-treatment. Patients with best-achieved eGFR above the median were more likely to have achieved an iSFLC of <20 mg/L (above median group 62% versus below median group 0%; p < .001) and lower best post-treatment iSFLC (20 (12-90) versus 67 (29-146) mg/L; p < .05). Best-achieved iSFLC was a prognostic factor for superior eGFR following treatment for M-AKI. Despite low eGFR at diagnosis, contemporary anti-myeloma therapy can achieve significant recovery of kidney function.


Subject(s)
Acute Kidney Injury , Multiple Myeloma , Humans , Prognosis , Renal Dialysis , Kidney , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multiple Myeloma/therapy , Glomerular Filtration Rate , Retrospective Studies
18.
BMC Nephrol ; 24(1): 145, 2023 05 24.
Article in English | MEDLINE | ID: mdl-37226096

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of several cancers. Pembrolizumab is an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody that is approved for the treatment of metastatic non-small cell lung cancer (NSCLC). Pembrolizumab-associated renal toxicity is relatively rare, even in pembrolizumab-associated glomerulonephritis. In this study, we report a rare case of pembrolizumab-induced C3 glomerulonephritis (C3GN) and RBC cast nephropathy. CASE PRESENTATION: A 68-year-old man with NSCLC was receiving treatment with pembrolizumab. After 19 cycles of pembrolizumab therapy, he presented with gross hematuria, severe lower-limb edema and oliguria. Laboratory tests revealed hypoalbuminemia, increased serum creatinine and low serum C3 level. Renal biopsy revealed a typical membranoproliferative glomerulonephritis accompanied by remarkable RBC casts in tubular cavities and tubulointerstitial infiltration of CD8-positive lymphocytes. Based on C3-only immunofluorescence deposit on glomeruli, a diagnosis of C3GN was made. Pembrolizumab was considered the cause of C3GN. Pembrolizumab was discontinued immediately, and 60 mg/day of prednisone was initiated. One dose of cyclophosphamide (400 mg, IV) was also administered. Upon treatment, his symptoms improved rapidly and serum creatinine decreased a lot. However, the patient became dialysis dependent eventually. CONCLUSION: This is the first case of C3GN with RBC cast nephropathy caused by ICIs. This rare case caused by the prolonged use of pembrolizumab further strengthens the relationship between ICIs and C3GN. Thus, periodic evaluation of urine and renal function is recommended in patients receiving pembrolizumab and other ICIs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Glomerulonephritis , Kidney Diseases , Lung Neoplasms , Male , Humans , Aged , Creatinine , Renal Dialysis , Glomerulonephritis/chemically induced , Glomerulonephritis/diagnosis
19.
Cureus ; 15(3): e35779, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37025735

ABSTRACT

Bile cast nephropathy (BCN) or cholemic nephrosis (CN) is a form of acute renal dysfunction that occurs in the setting of hepatic dysfunction and hyperbilirubinemia. We present a case of a 58-year-old woman with a four-day history of intractable nausea, vomiting, and yellowish discoloration of her skin and eyes. Laboratory workup was notable for elevated total bilirubin (mainly direct), liver enzymes, creatinine, and blood urea nitrogen (BUN). The ultrasonography (US) of the abdomen showed hepatic steatosis. The hepatitis panel was remarkable for hepatitis A IgM. She was initially treated with supportive therapy. However, her bilirubin levels reached over 20 mg/dl, creatine was >8 mg/dl, and her estimated glomerular filtration rate (eGFR) was <10. Kidney biopsy showed pigmented casts consistent with BCN. She was started on hemodialysis with significant improvement in her symptoms and liver enzymes. This case underscores the importance of a broad differential diagnosis in cases with hyperbilirubinemia and acute kidney injury. BCN requires renal biopsy for a definitive diagnosis, and these patients usually require hemodialysis.

20.
Clin Case Rep ; 11(2): e6986, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36852120

ABSTRACT

Multiple myeloma (MM) results from malignant plasma cell disorder. It represents approximately 10% of hematological malignancies and it is typically diagnosed in the elderly with a median age of 70 years and has a steep increase in incidence with advancing age. N Engl J Med. 2004, 1860; Clin Interv Aging. 2020, 619. The incidence of MM has been increasing over time, mostly due to population aging. Mayo Clin Proc. 2010, 225 However, certain MMs are diagnosed at young age even under 40 years old (2%). Leuk Lymphoma. 1998, 493; Blood. 2010, 5501. We report a case of a MM in a thirty-four-year-old woman whose circumstance of discovery was acute kidney failure.

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