A Case of NELL-1-Positive Membranous Nephropathy With Acute Kidney Injury Due to Bilateral Renal Vein Thrombosis.

Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in non-diabetic adults. It can be primary, attributed to autoantibodies targeting podocyte antigens, or secondary to various disorders. Although rare, nerve epidermal growth factor-like 1 (NELL-1)-associated MN presents diagnostic and management challenges. Thrombotic complications such as renal vein thrombosis (RVT) are recognized but less reported, especially in NELL-1-positive MN. We report a 43-year-old male with NELL-1-positive MN complicated by acute kidney injury (AKI) due to bilateral RVT, treated successfully with thrombolysis. Histopathological analysis confirmed MN with specific immunohistochemical staining for NELL-1. Treatment included immunosuppressive therapy and tailored anticoagulation. This case emphasizes recognizing thrombotic complications in MN, particularly in NELL-1-positive cases. Further research is needed to explore serum anti-NELL-1 antibodies as biomarkers and optimal anticoagulation strategies in MN patients at risk of thrombotic events to improve outcomes and guide personalized management.

Bortezomib-Induced Superficial Vasculitis in a Kidney Transplant Recipient: A Rare Case.

Bortezomib is a frequently administered immunosuppressive agent in kidney transplantation. A 30-year-old male kidney transplant recipient developed an atypical reaction on the left hand in terms of spider-like extensions, indicating erythematous inflammation along the superficial veins after bortezomib intravenous administration. The inflammation spontaneously resolved after three weeks with a bortezomib dose reduction. Nephrologists must be familiar with the potential cutaneous bortezomib-induced adverse effects.

Dapagliflozin-Induced Erythrocytosis in Chronic Kidney Disease: A Rare Occurrence.

Erythrocytosis, a rare adverse effect associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), has been reported in diabetic patients, but its occurrence in those with chronic kidney disease (CKD) remains underrecognized. Here, we present two cases of dapagliflozin-related erythrocytosis in diabetic patients with CKD, highlighting the need for increased awareness among clinicians. Despite the established efficacy of SGLT2i in managing type 2 diabetes mellitus (T2DM) and its cardiovascular benefits, erythrocytosis poses a potential complication, necessitating thorough understanding and monitoring. While the precise mechanism of SGLT2i-induced erythrocytosis remains unclear, hypotheses include hemoconcentration and modulation of iron metabolism. Notably, our cases demonstrate a rapid onset of erythrocytosis, possibly exacerbated by CKD, emphasizing the importance of vigilant hemoglobin monitoring, especially in CKD patients on SGLT2i therapy. Timely discontinuation of dapagliflozin resulted in a significant reduction in hemoglobin levels, underscoring the critical role of early intervention in preventing erythrocytosis-related complications. This report advocates for routine hematological evaluation in CKD patients treated with SGLT2i to promptly detect and manage erythrocytosis, enhancing patient safety and improving clinical outcomes.

Nephrotic Syndrome Due to Sunitinib: A Rare Complication of Treatment of Renal Cell Carcinoma.

This case report details a 62-year-old male with a history of right renal cell carcinoma (RCC) who developed sunitinib-induced nephrotic syndrome during treatment. The patient had a complex medical history, including a right nephrectomy in 2009, brain metastasis excisions in 2011 and 2012, and prolonged sunitinib therapy. Hypothyroidism, hypertension, and various surgeries further complicated his clinical picture. In April 2022, the patient presented with bilateral pedal edema, acute kidney injury superimposed on chronic kidney disease, and proteinuria. Upon examination, the decision was made to discontinue sunitinib, leading to the resolution of nephrotic syndrome. Adjustments in thyroxine dosage were made, and pharmacological interventions were employed to manage proteinuria and renal dysfunction. A multidisciplinary approach involving oncologists, nephrologists, and endocrinologists was essential in achieving a favorable outcome. The case highlights the intricate balance required in managing patients undergoing targeted cancer therapies, emphasizing the importance of vigilant monitoring, prompt intervention, and a collaborative approach for optimal patient care.

A Rare Case of Autoimmune Disorder as a Trigger for Atypical Hemolytic Uremic Syndrome.

Autoimmune diseases may act as a trigger for atypical hemolytic uremic syndrome (aHUS). Triggers for aHUS may include autoimmune diseases, infections, metabolic conditions, pregnancy, and transplants. aHUS-mediated injury to various organs, especially kidneys, can be life-threatening. Here, we present the case of a young female who had perinuclear antineutrophil cytoplasmic antibody (p-ANCA)-associated vasculitis and was diagnosed with aHUS. We consider underlying autoimmune p-ANCA-associated vasculitis as a trigger for aHUS in this case.

A Rare Case of Atypical Anti-glomerular Basement Membrane Disease.

Anti-glomerular basement membrane (Anti-GBM) disease is a severe form of glomerulonephritis (GN) that predominantly impacts individuals aged 20 to 70. It arises from the presence of circulating antibodies that specifically target an antigen inherent to the basement membranes of glomerular and alveolar structures. A unique subset within this category is termed atypical anti-GBM disease. In this variant, a distinctive feature is the widespread linear staining of the glomerular basement membrane (GBM) by IgG observed through immunofluorescence microscopy, with the notable absence of anti-GBM antibodies in the patient's serum. Here, we present an unusual case involving a 65-year-old female patient who sought medical attention due to rapidly progressing renal failure. The initial management included six hemodialysis sessions. Following a kidney biopsy, the diagnosis revealed a sclerosed phase of diffuse crescentic glomerulonephritis, attributed to atypical anti-GBM disease. Given the presence of diffuse crescents on the kidney biopsy, the medical team opted for an aggressive treatment regimen, commencing with intravenous methylprednisolone, followed by oral cyclophosphamide and oral prednisolone. Plasmapheresis was also recommended as part of the treatment plan, although it did not materialize due to the family's reluctance. Despite exhaustive efforts, the renal failure exhibited no signs of improvement, leading to the patient's discharge with a plan for ongoing maintenance hemodialysis. It is crucial to emphasize the pivotal role of immunosuppressive medications in managing this condition, as they play a critical role in preventing antibody formation and subsequent hypersynthesis that can exacerbate the disease.

Young Male With End-Stage Renal Disease Due to Primary Hyperoxaluria Type 2: A Rare Presentation.

Primary hyperoxaluria type 2 (PH2) is a rare genetic disorder characterized by excessive oxalate production due to glyoxylate metabolism alterations. This case report presents a 26-year-old male with PH2 who experienced recurrent nephrolithiasis since childhood, leading to end-stage renal disease (ESRD). The patient's history prompted genetic testing, which revealed a heterozygous missense variant in the GRHPR gene, confirming PH2. Early genetic diagnosis is crucial for preventing ESRD and planning effective treatments. Patients with PH2 require intensive hemodialysis and may benefit from kidney transplantation. However, even after transplantation, ongoing preventive measures are essential due to the risk of hyperoxaluria-related graft damage. This case highlights the importance of early detection and genetic testing in managing PH2 to delay ESRD and improve patient outcomes.

Nephrotic Syndrome in a Retroviral Disease Due to AA Amyloidosis: A Rare Presentation.

Kidney disease poses a significant burden on individuals with HIV infection. In the pre-ART era, HIV-associated nephropathy (HIVAN) was the most common renal pathology identified in individuals with HIV. However, the widespread use of ART has led to changes in the spectrum of renal pathologies associated with HIV. HIV infection is an unclear cause of AA amyloidosis. Here, we report a rare case of an HIV-positive patient presenting with nephrotic syndrome which turned out to be AA amyloidosis on renal biopsy.

Lupus Nephritis With Collapsing Glomerulopathy: A Rare Association.

Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Crescentic lupus nephritis rarely presents as rapidly progressive renal failure (RPRF) and needs prompt initiation of treatment. Collapsing glomerulopathy (CG) itself is associated with poor renal survival. Collapsing glomerulopathy's association with lupus nephritis is rarely reported in the literature. It may indicate a severe form of lupus podocytopathy.

A Case of End-Stage Renal Disease With Hemifacial Swelling.

A 64-year-old male, with end-stage renal disease on maintenance hemodialysis twice a week for the last two years, presented with swelling over the left half of his face, left side of the neck, and left upper limb for two months. The vascular access for hemodialysis was the left brachiocephalic arteriovenous (AV) fistula. There was no history of insertion of a dialysis catheter on the left side of the neck. Physical examination showed dilated and tortuous veins over the left side of his chest and left arm with normal-functioning AV fistula. Computed tomography (CT) venogram revealed narrowing in the left brachiocephalic vein and cephalic vein with multiple collaterals in the left upper limb and shoulder region. Ballon angioplasty was done across the stenotic segments, and a good flow was achieved with no remnant stenosis. This is a rare presentation as there was no history of cannulation of left-sided central vessels.

ABO Incompatible Kidney Transplant in a Patient With Atypical Hemolytic Uremic Syndrome: Case Report.

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection. Graft acceptance was facilitated by triple immunosuppression (steroid, tacrolimus, and mycophenolate mofetil), and 4-month serum creatinine follow-up indicated the absence of antibody-mediated rejection and recurrence of aHUS. This case demonstrates that in patients with aHUS, ABOi renal transplant can be performed successfully.

Kidney Transplant Outcomes in Patients with Atypical Hemolytic Uremic Syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder with a high probability of recurrence after a kidney transplant and can adversely affect the graft outcome. Our objective was to assess the transplant outcome of patients with aHUS who had undergone a kidney transplant. METHODS: We retrospectively included patients who had undergone a kidney transplant and been diagnosed with aHUS based on an anti-complement factor H (AFH) antibody level >100 AU/mL and the presence of a genetic abnormality in complement factor H (CHF) or CHF-related (CFHR) genes. Data were analyzed with descriptive statistics. RESULTS: Among 47 patients with AFH antibody levels >100 AU/mL, 5 (10.6%) had undergone a kidney transplant. The mean age was 24.2 years, and all were male. Atypical hemolytic uremic syndrome was diagnosed before transplant in 4 (80.0%) cases, whereas 1 was diagnosed after transplant owing to disease recurrence in the transplanted graft. Genetic analysis of all cases revealed one or more abnormalities in CFH and CFHR genes 1 and 3. With an average of 5 sessions of plasma exchange and the use of rituximab in 4 cases, there was a reduction in the disease severity with no recurrences in the post-transplant period. At the latest follow-up of 223 days, the mean serum creatinine level was 1.89 mg/dL, indicating good graft function. CONCLUSIONS: Among patients diagnosed with aHUS, the use of pre-transplant plasma exchange and rituximab can be beneficial in terms of preventing graft dysfunction and reducing disease recurrence in the post-transplant period.

Profile and Post-Kidney Retrieval Outcomes in Asymptomatic Kidney Donors With Genetic Mutations in Complement Factors-Related Genes.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder triggered by various stressors. Most of the time, stressors may not be identified in patients with aHUS. The disease may remain quiescent without manifestation throughout life. BACKGROUND: To assess the outcome of an asymptomatic carrier of genetic mutations of patients with aHUS who had undergone donor kidney retrieval surgery. METHODS: We retrospectively included the patients diagnosed with a genetic abnormality in complement factor H (CHF) or CHF-related (CFHR) genes without manifestation of the aHUS and who had undergone donor kidney retrieval surgery. The data were analyzed with descriptive statistics. RESULTS: Among patients who were the kidney recipients from the prospective donors, 6 donors were screened for genetic mutations in CFH and CFHR genes. Four donors showed positive mutation for CFH and CFHR. The mean age was 54.5 years (range, 50-64 years). After over a year since donor kidney retrieval surgery, all prospective mother donors are alive without aHUS activation and with a normal kidney function on a single kidney. CONCLUSION: Asymptomatic carriers of genetic mutations in CFH and CFHR can be the prospective donors for their first-degree family member who have active aHUS. A genetic mutation in an asymptomatic donor should not be a contraindication for refuting the prospective donor.

CYP3A5 Polymorphism in Renal Transplantation: A Key to Personalized Immunosuppression.

BACKGROUND: Tacrolimus is essential for the maintenance of immunosuppression after a kidney transplant. CYP3A5 is the gene that metabolizes tacrolimus, and polymorphism in this gene affects the metabolizing status. AIM: To assess the genetic polymorphism status of patients undergoing kidney transplantation and determine its impact on graft function and complications in the post-transplant period. METHODS: We retrospectively included the patients who had undergone a kidney transplant and had positive genetic polymorphism of the CYP3A5 gene. Based on loss of alleles, patients were categorized as non-expresser (loss of both alleles), intermediate expresser (loss of one allele), and expresser (no loss of allele) denoted by CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively. Data were analyzed with descriptive statistics. RESULTS: Of 25 patients, 60%, 32%, and 8% were non-expressers, intermediate-expressers, and expressers, respectively. The mean tacrolimus trough concentration to dose ratio after 6 months of the transplant was higher in non-expressers than intermediate-expressers and expressers (213 vs 85 and 46 ng/mL/mg/kg/d, respectively). The graft function was normal in all 3 groups except for graft rejection 1 patient in the expresser group. Compared with expressers, urinary tract infections (42.9% and 62.5%) and new-onset diabetes after transplantation (28.6% and 12.5%) were more frequent in non-expresser and intermediate expressers, respectively. The proportion of patients developing new-onset diabetes after transplantation was lower with the pre-transplant diagnosis of CYP3A5 polymorphism (16.7% vs 23.1%). CONCLUSION: Genotype-based dosing of tacrolimus helps achieve the desired therapeutic concentrations that can help to optimize graft outcomes and reduce the tacrolimus-related adverse effects. Pre-transplant evaluation of CYP3A5 can be more helpful in planning treatment strategies for optimized outcomes after kidney transplantation.

Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVES: Maintenance hemodialysis (MHD) patients are at increased risk of contracting coronavirus disease 2019 (COVID-19). Vaccine against COVID-19 offers the benefit of protection from severe illness. In this study, we assessed the humoral response after two doses of the COVISHIELDTM vaccine in MHD patients. MATERIALS AND METHODS: In a prospective cohort study, the humoral response with two doses of the COVISHIELDTM vaccine was assessed after 14 ± 2 days of the second dose. The COVIPROTECT antibody titers against the spike protein were measured using the electrochemiluminescence immunoassay (ELECSYS, Roche Diagnostics International Ltd.). Data were analyzed to determine the predictors of antibody response. RESULTS: Between February and October 2021, 50 MHD patients were assessed. The mean age was 55.8 ± 10.8 years, and 72% were males. A total of 48 (96%) MHD patients have seropositivity. The median level of spike protein antibody was 579 U/mL [interquartile range (IQR25-75) 166-1852.75]. Compared to patients with no COVID-19 infection history, the median levels of antibodies were significantly higher in those with a history of COVID-19 (1047 vs 297 U/mL, p = 0.011). The antibody titers did not differ by age (p = 0.269), presence of comorbidities such as hypertension (p = 0.341), diabetes mellitus (p = 0.719) or ischemic heart disease (IHD) (p = 0.695), dialysis vintage (p = 0.660), and timing of diagnosis of COVID-19 in relation to vaccination (p = 0.261). Adverse events (AEs) occurred in one-third of patients that were mild and self-limiting. No serious AEs were observed in any patient. CONCLUSION: In MHD patients, two doses of the COVISHIELDTM vaccine induced a substantial humoral response. Prior history of COVID-19 resulted in a higher antibody response. Thus, the COVISHIELDTM vaccine is efficacious and safe for use in patients with MHD. How to cite this article: Balwani MR, Pasari AS, Bawankule C, et al. Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis. J Assoc Physicians India 2023;71(9):56-60.

Spectrum of Biopsy-proven Native Kidney Disease in Central India.

Spectrum of native renal biopsy reports varies geographically. Here, we tried to determine the prevalence of renal biopsy disorders and compare it with other studies. Retrospective study was performed at Saraswati Kidney Care Center, Nagpur and Jawaharlal Nehru Medical College, Sawangi, India. All the native kidney biopsies from January 2017 to March 2020 were included in the analysis. Demographic details of all the patients were recorded. Renal diseases were classified as glomerular, tubulo-interstitial, predominant vascular involvement and other disease categories. Total 347 native kidney biopsies were performed during the study period. Mean age of the patients at the time of biopsy was 41.41 ± 15.75 years. Majority of patients were males (58.5%). Most common indication for kidney biopsy was nephrotic syndrome (36.3%) followed by nephritic syndrome (19.9%). Among the glomerular diseases (GDs), 69% were primary glomerulopathies and 31% were secondary GDs. Immunoglobulin (IgA) nephropathy (30.85%) was the most common primary GD followed by membranous nephropathy (MN) (26.59%), focal segmental glomerulosclerosis (FSGS) (17.02 %) and minimal change disease (14.36 %). Among secondary glomerulopathies, lupus nephritis was the most common histopathological diagnosis (31.8%) followed by diabetic nephropathy (26.1%), amyloidosis (17%), infection related glomerulonephritis (11.3%), light chain deposition disease (4%) and anti-neutrophil cytoplasmic antibody associated vasculitis (3.4%). In tubulointerstitial disease, 33.3% had acute tubulointerstitial nephritis, whereas each 26.6% had acute tubular injury and cast nephropathy. The most prevalent diagnosis in our only study from central India was IgA nephropathy followed by MN and FSGS. Data analysis at regular intervals helps in understanding the changing trend of prevalence of native kidney disease and also gives understanding of geographical variations.

Clinical and Histopathological Profile of Immunoglobulin A Nephropathy Patients in Central Part of India: A Single-Center Study.

The objective of the study was to assess clinical and histopathological profile of patients who were diagnosed as immunoglobulin A nephropathy (IgAN) on renal biopsy. Medical data were collected for this retrospective study at a single center from patients with biopsy-proven IgAN, from those biopsied between January 2017 and September 2020. A total of 347 renal biopsies were performed during the study. There were 52 patients with primary IgAN who met our inclusion criteria. Males were more commonly affected (61.5%). The mean age at the time of kidney biopsy was 35.26 ± 10.39 years. Hypertension was present in 84.5% of patients. Median serum creatinine and estimated glomerular filtration rate (eGFR) at presentation were 3.58 mg/dL and 15.8 mL/min/1.73 m2, respectively. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/ interstitial fibrosis (T1/T2), and crescents (C1/C2) were present in 46.2%, 38.5%, 88.5%, 75% and 36.6% of patients respectively. Thrombotic microangiopathy (TMA) and hypertensive vasculopathy were seen in 38.5% and 86.5% of patients respectively. The presence of tubular atrophy (T1/T2), hypertensive vasculopathy, and TMA on renal biopsy was significantly associated with low eGFR at presentation whereas no such correlation could be established with segmental glomerulosclerosis (S1), crescents (C1/C2), mesangial (M1) and endocapillary hypercellularity (E1). The presence of hypertensive vasculopathy and TMA on renal biopsy was associated with poor renal function at presentation. The most common clinical presentation of IgAN was hypertension and so we suggest patients with hypertension should be screened for microscopic dysmorphic hematuria and proteinuria, if present, should undergo a renal biopsy to diagnose this disease in early stages.

Impact of COVID-19-associated Mucormycosis in Kidney Transplant Recipients: A Multicenter Cohort Study.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is a recently emerging entity. There is a lack of reports of CAM in organ transplant recipients. METHODS: We conducted a multicenter (n = 18) retrospective research in India during November 2020 to July 2021. The purpose of this study was to explore the clinical spectrum, outcome and risk factors for mortality of CAM in kidney transplant recipients (KTRs). RESULTS: The incidence of CAM was 4.4% (61/1382 COVID-19-positive KTRs) with 26.2% mortality. The median age of the cohort was 45 (38-54) y. Twenty (32%) were not hospitalized and 14 (22.9%) were on room air during COVID-19. The proportion of postdischarge CAM was 59.1%, while concurrent CAM was reported in 40.9%. The presentation of CAM was 91.8% rhino-orbital-cerebral mucormycosis and 8.2% pulmonary with 19.6% and 100% mortality, respectively. In the univariable analysis, older age, obesity, difficulty of breathing, high-flow oxygen requirement, and delay in starting therapy were significantly associated with mortality. In the multivariable logistic regression analysis, patients requiring high-flow oxygen therapy [odds ratio (95% confidence interval) = 9.3 (1.6-51); P = 0.01] and obesity [odds ratio (95% confidence interval) = 5.2 (1-28); P = 0.05] was associated with mortality. The median follow-up of the study was 60 (35-60) d. CONCLUSIONS: We describe the largest case series of CAM in KTRs. Morality in pulmonary CAM is extremely high. Severe COVID-19 pose extra risk for the development of CAM and associated mortality. Our report will help in better understanding the conundrum and management of CAM.