Drug-Induced Podocytopathies: Report of Four Cases and Review of the Literature.

Kidney injury due to medications is a well-known clinical entity. Although drug-induced tubulointerstitial disease is commonly encountered, there are few reports in the literature associated with glomerular injury due to medications. The recognition of this type of kidney injury is crucial, as rapid discontinuation of the offending agent is critical to maximizing the likelihood of quick and effective renal function recovery. In this article, we present four cases that presented with nephrotic syndrome and were diagnosed with biopsy-proven podocytopathies, associated with exposure to a certain medication. All of them experienced complete resolution of nephrotic syndrome within days or weeks after discontinuation of the offending drug. We also present the data, which were found in a Medline search from the year 1963 until the present, regarding cases with podocytopathies associated with penicillamine, tamoxifen and the combination of pembrolizumab-axitinib, including only adult cases from the English literature. The Medline search revealed nineteen cases of penicillamine-induced minimal-change disease (MCD), one case of tamoxifen-induced MCD, and none associated with pembrolizumab-axitinib therapy. We also searched for the largest studies and meta-analyses regarding drug-induced podocytopathies after a Medline search from 1967 to the present of the English literature.

Treatment of HIV-Associated Lupus-like Membranous Nephropathy with Tacrolimus: A Case Report and Review of the Literature.

Renal complications of HIV infection are common and histologically diverse. Besides HIV-associated nephropathy, which is the most well-defined glomerular disorder, immune-complex-mediated glomerulonephritis (HIVICK) is also encountered in the setting of HIV infection and may occasionally present with "lupus-like" features by light microscopy and immunofluorescence. Management of HIVICK remains controversial and mainly focuses on HIV viremia suppression with combined antiretroviral therapy. Immunosuppressive therapy may be used in order to mitigate the renal inflammation induced by the immune complex deposition. Data regarding the use of immunosuppressants in HIVICK are very limited, mostly including corticosteroids and mycophenolate acid analogues. Herein, we present the case of a 40-year-old HIV-infected Caucasian man with nephrotic syndrome, renal impairment, and a "lupus-like" membranous pattern in the kidney biopsy, who achieved a partial response of his proteinuria with a tacrolimus-based regimen in combination with antiretroviral therapy.

Pregnancy in Women With Preexisting Glomerular Diseases: A Single-Center Experience.

AIM: Women with glomerular diseases are often of childbearing age. Besides lupus nephritis, data regarding pregnancy in patients with glomerular diseases are limited, posing a challenging task to attending nephrologists. This study aimed to investigate the pregnancy outcomes and the impact on the underlying glomerular disease among women followed in our institution. METHODS: A single-center retrospective cohort study of women with biopsy-proven glomerular diseases who experienced pregnancy between 2010 and 2020. We analyzed data before, during, and after gestation. RESULTS: A total of 22 women, 13 women with primary and 9 women with secondary glomerular diseases, were included in this study. Most patients (82%) had received immunosuppressive treatment at various times before pregnancy. All the women were in remission, either complete (62%) or partial (38%), with well-preserved renal function (82%) before conception. A total of 30 live births and 1 stillbirth were recorded; the rate of preterm delivery was 23%. Renal function and proteinuria remained stable during pregnancy. Preeclampsia was observed in 6.7% of patients and disease relapse in 6.9% of the pregnancies. CONCLUSION: Pregnancy was associated with a low frequency of adverse events in women with underlying glomerular diseases, provided they have quiescent disease and preserved renal function.

The diagnosis and management of sarcoid-like reactions in patients with melanoma treated with BRAF and MEK inhibitors. A case series and review of the literature.

Sarcoidosis and sarcoid-like reactions (SLR) have been repeatedly reported in patients with melanoma treated with BRAF and MEK inhibitors. In the current study we present three patients that developed SLR under treatment with BRAF and mitogen-activated protein kinase (MEK) inhibitors for melanoma. Two patients developed mediastinal lymphadenitis with histological features of an SLR while on targeted therapy in the adjuvant setting, whereas one patient with metastatic melanoma developed granulomatous nephritis while receiving combination treatment with BRAF/MEK inhibitors and atezolizumab. In addition, we review the published literature on the pathogenesis, clinical characteristics, histologic features, imaging findings, and other potential useful diagnostic tools. We also address the need for a common terminology for these cases and propose an algorithm for the accurate diagnosis of BRAF/MEK inhibitor-induced SLR. We also review the currently available data on the treatment of these patients and suggest a treatment approach for SLR in patients with melanoma, as well as for the management of melanoma when SLR emerges.

Clinicopathologic features and treatment outcomes of patients with fibrillary glomerulonephritis: A case series.

ABSTRACT: Fibrillary glomerulonephritis (FGN) is a diverse glomerular disease with poor renal prognosis. The optimal therapeutic approach remains undetermined, as treatment outcomes vary across different studies.We retrospectively reviewed the medical data of 10 patients diagnosed with biopsy-proven FGN at our center between 2004 and 2019. Clinical and histological features, as well as therapeutic regimens and treatment response, are reported.The patients were predominantly men (2.5/1 men-female ratio) with a mean age at diagnosis of 46.5 years (IQR: 41.5-59.5). The median proteinuria and creatinine levels at presentation were 2.55 g/day (IQR: 0.4-8.9) and 1.35 mg/dl (IQR: 0.94-1.88), respectively. Four out of 10 patients presented with nephrotic syndrome, 5 patients with nephritic syndrome and 1 with isolated microscopic hematuria. Light microscopy showed mesangial proliferative (n = 7), membranoproliferative-like (n = 2), and diffuse sclerosing patterns (n = 1). Rituximab was used in 7/10 patients, either as monotherapy (n = 3) or combined with cyclophosphamide and corticosteroids (n = 4). Patients who were treated with immunosuppression had higher median levels of creatinine (1.40 mg/dl) and proteinuria (3.5 g/d) compared to those who received supportive treatment alone (0.94 mg/dl and 0.6 g/d, respectively). After a median follow-up of 30 months (IQR:18-66.5), 4 out of 7 patients (57%) treated with immunosuppression achieved a clinical response, 1 had persistent renal dysfunction and 2 patients progressed to end-stage renal disease.The present case series extends the existing literature on the clinical features and outcomes of FGN, as well as the use of rituximab-based regimens for the treatment of the disease. Further research is needed to establish the proper management of the disease.

Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience.

Focal Segmental Glomerulosclerosis (FSGS) recurrence after kidney transplantation (KTx) is relatively frequent and is associated with poor graft survival. The aim of this study was to investigate which management strategies were associated with better outcomes in our cohort of KTx recipients with primary FSGS. We retrospectively collected data on patients with primary FSGS who received a KTx between 1993 and 2019. A history of biopsy proven FSGS in native kidneys and new onset of significant proteinuria early post-KTx led to the diagnosis of recurrence, which was confirmed by graft biopsy. From 1993 to 2019 we performed 46 KTxs in patients with primary FSGS. We identified 26 episodes of recurrence in 25 patients, 67% of them occurring in males. They were younger at the time of KTx (33.8 vs. 41.1 years old, p = 0.067) and had progressed to end stage renal disease (ESRD) faster after FSGS diagnosis (61.4 vs. 111.2 months, p = 0.038), while they were less likely to have received prophylactic plasmapheresis (61.5% vs. 90%, p = 0.029). 76.7% of recurrences were found early, after a median of 0.5 months (IQR 0.1-1) with a median proteinuria was 8.5 (IQR 4.9-11.9) g/day. All patients with recurrence were treated with plasmapheresis, while 8 (30.7%) additionally received rituximab, 1 (3.8%) abatacept, and 4 (15.4%) ACTH. 7 (27%) patients experienced complete and 11 (42.3%) partial remission after a mean time of 3 (±1.79) and 4.4 (±2.25) months, respectively. Prognosis was worse for patients who experienced a recurrence. Eleven (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5-43.3) months. In this series of patients, primary FSGS recurred frequently after KTx. Prophylacic plasmapheresis was shown efficacious in avoiding FSGS recurrence, while timely diagnosis and plasmapheresis-based regimens induced remission in more than half of the patients.

De Novo Minimal Change Disease following Vaccination with the Pfizer/BioNTech SARS-CoV-2 Vaccine in a Living Kidney Donor.

Coronavirus disease 2019 has developed as a pandemic. Immunization with the introduction of vaccines against COVID-19 seems be the only way to end this pandemic. We report on a case of a kidney donor, who developed minimal change disease (MCD) within 4 days post-vaccination with the SARS-CoV-2 BNT162b2 mRNA vaccine (Pfizer/BioNTech). She donated her kidney to her husband 4 years ago. After receiving the 1st vaccine dose, she presented with nephrotic syndrome, with complete remission 5 days later. She proceeded with the second dose of the BNT162b2 vaccine at the appointed time. Two days later, she presented with a relapse of full-blown nephrotic syndrome with preserved renal function. We performed an ultrasound-guided percutaneous kidney biopsy and the final diagnosis was consistent with minimal change disease. Oral prednisolone was promptly initiated at a dosage of 1 mg/kg daily and complete remission was achieved 10 days later. More data about this rare appearance of de novo glomerular diseases after SARS-CoV-2 vaccination are emerging and should be interpreted rigorously.

A case report of hypocomplementemic urticarial vasculitis presenting with membranoproliferative glomerulonephritis.

BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. CASE PRESENTATION: We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. CONCLUSIONS: The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.

A Patient with Cryoglobulinemic Membranoproliferative GN (MPGN) Who Survived COVID-19 Disease: Case Presentation and Current Data of COVID-19 Infection in Dialysis and Transplanted Patients in Greece.

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Case of an unusual diagnosis of primary antiphospholipid syndrome with multiple clinical complications.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by the presence of antiphospholipid antibodies in association with thrombotic events and/or obstetric complications. Renal involvement is not infrequent in both primary and secondary APS. Kidney manifestations comprise a wide range of clinical features, including hypertension, major renal vessel thrombosis or microvascular endothelial injury, also described as APS nephropathy. In the absence of a thrombotic event, clinical manifestations of APS are often non-specific. We recently encountered a case of primary APS in a young male with newly diagnosed hypertension and renal impairment. The diagnosis of APS was initially suspected by his kidney biopsy findings, when electron microscopy examination showed the features of chronic microangiopathy, and was later confirmed by a triple positive antiphospholipid antibody profile and multiple organ involvement.

Clinical impact of repeat renal biopsies in patients with lupus nephritis: Renal biopsy is essential especially later in the course of the disease.

OBJECTIVE: The clinical impact of repeat renal biopsies in patients with lupus nephritis (LN) is still debatable. The aim of this retrospective analysis was to assess whether repeat renal biopsy is a reliable tool in guiding therapeutic decisions. METHODS: Laboratory and histological parameters and therapeutic changes in 35 patients with LN and repeat renal biopsies were retrospectively analyzed. Biopsies were performed in the presence of clinical evidence of an active glomerular disease. Biopsy specimens were retrospectively re-assessed by two renal pathologists and were compared according to the last International Society of Nephrology/ Renal Pathology Society classification. RESULTS: Thirty-five patients had two, 13 had three, 5 had four, 4 had five, and 1 had six renal biopsies. Fifty-eight comparisons of renal biopsies were made. Median times between the first and second, second and third, third and fourth, and fourth and fifth biopsies were 31, 27, 34, and 28 months, respectively. The mean activity indices from the first to the fifth biopsy were 8.7, 6.6, 7.8, 9.4, and 4.7, whereas the mean chronicity indices were 1.7, 2.3, 4.3, 5.2, and 7.7, respectively. Conversion was observed in 65.5% of cases with the most frequent (21%) being between classes III and IV. Conversion to a more severe type of nephritis occurred in 19% of cases. There was no correlation of laboratory parameters to the type of nephritis upon conversion. In 79% of cases, immunosuppressive therapy was modified after repeat biopsy. CONCLUSION: Repeat biopsy is a reliable tool for monitoring the activity and chronicity status of LN and for tailoring immunosuppressive therapy to the needs of the patient, especially late in the course of the disease.

Colchicine in Renal Diseases: Present and Future.

Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty arthritis and familial Mediterranean fever. In this review, we summarize current and potentially future pharmacologic activities of colchicine in various renal disease entities along with pharmacokinetic and pharmacodynamic properties. Additionally, we will refer to main interactions of colchicine with medications used in renal medicine, as well as dosing recommendations in patients with reduced glomerular filtration rate.

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience.

OBJECTIVES: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.

Excellent long term patient and renal allograft survival after ABO-incompatible kidney transplantation: Experience of one center.

AIM: To investigate the long-term results of ABO-incompatible (ABOi) kidney transplantation in a single center in Greece. METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B IgG antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus (TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible (ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the follow-up period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications. RESULTS: The mean follow-up period was 6 years (range 1 to 9 years). A mean of 5.0 ± 3.0 (range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly (100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points (100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibody-mediated rejection evidenced by histological signs. Four patients (13.3%) in the ABOi group and 3 (10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups. CONCLUSION: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceased-donor waiting lists.

Kidney transplantation in patients with systemic lupus erythematosus.

Despite improvements in overall prognosis in lupus nephritis, 10%-30% of patients with proliferative renal involvement progress to end stage renal disease, according to the severity of the disease and associated socioeconomic factors. Kidney transplantation has been recognized as the most appropriate treatment for those patients, but several issues remain after renal function restoration in a lupus recipient. Among these are the fear of lupus nephritis recurrence in the graft, the choice of immunosuppressive therapy in cases of recurrent lupus for a patient who has already received a toxic and prolonged immunosuppressive course, and finally, the management of comorbidities to reduce associated morbidities in the long term. All the above topics are examined in this review, with the hope of providing a clear picture of data as illustrated in the current literature.

Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.

Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

Kidney transplantation outcomes from expanded criteria donors, standard criteria donors or living donors older than 60 years.

OBJECTIVES: To evaluate outcomes in kidney allograft recipients from donors with expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60 years. METHODS: We studied all patients who received a kidney between 2005 and 2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years. ECD was any deceased donor >60 years or >50 years with two of the following: hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5 mg/dL. We recorded characteristics of the transplant procedure, patient, graft survival and renal function 1 year after transplantation and at the end of follow-up. RESULTS: Six-hundred and five patients were transplanted between 2005 and 2011 in our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%) from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time of 36.4 months, graft survival rates were similar for all groups. Calculated GFR was found statistically different between the ECD and SCD groups, but still satisfactory at first year, and at end of follow-up time. Comparison of the patients, who received transplants from ECD, even older than 70 years, and those from LD >60 years revealed equivalent renal function in short and long term. CONCLUSIONS: Utilization of marginal kidneys effectively doubled our deceased transplant volume in the period 2005-2011. Patients' and graft survival were shown similar at the end of follow-up for all groups. Renal outcomes were shown equivalent between the ECD and LD >60 years groups, and although significantly lower between the ECD and the SCD group, were still very satisfactory.

Histological spectrum of mycophenolate mofetil-related colitis: association with apoptosis.

AIMS: The main purpose of this study was to define diagnostic histological characteristics of mycophenolate mofetil (MMF)-related colitis in association with crypt epithelial cell turnover. METHODS AND RESULTS: The examined material included 43 colonic biopsies from renal transplant recipients with MMF administration and persistent diarrhoea. Thirty-three cases showed MMF-related colitis, while 10 showed no significant changes. The histological findings were scored and correlated with the apoptotic index (AI) and with the proliferation rate (PR) of the crypt epithelium examined by TUNEL assay and Ki-67 immunoexpression. Ten cases of Crohn disease and 10 of ulcerative colitis were used as comparative groups. Crypt distortion and loss as well as increased apoptosis constituted the main features, their degree and combination leading either to an inflammatory bowel disease (IBD)-like (82%) or to a graft-versus-host disease-like pattern (18%). A high AI was associated more frequently with moderate and severe crypt distortion, while the values were significantly higher compared with the control groups (P < 0.01). High PR was noted in 18 of 29 (62.1%) of the cases. CONCLUSIONS: The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.

Depletion of B lymphocytes in idiopathic membranous glomerulopathy: results from patients with extended follow-up.

AIMS: To assess the long-term therapeutic benefit of temporary depletion of B lymphocytes in patients with idiopathic membranous glomerulopathy (MGN) and search for potential predictors of response. PATIENTS AND METHODS: The patients included had been diagnosed with biopsy-proven MGN in the absence of secondary causes. Estimated glomerular filtration rate should be above 30 ml/min/1.73 m(2) and 24-hour proteinuria 3 g/day or more. Patients who had been treated with cyclosporine or cytotoxic agents the year prior to study entry were excluded. Depletion of B cells was achieved with rituximab, which was administered intravenously for 4 consecutive weeks. Partial remission was defined as a >50% decrease in proteinuria with absolute proteinuria <3 g/day, while complete remission was defined as a >50% decrease in proteinuria and an absolute protein excretion <0.3 g/day. RESULTS: Twelve patients were studied (4 females/8 males) with a mean age of 51.3 years. No major adverse effects were observed. During a median follow-up time of 48 months, 11/12 (91.6%) patients achieved remission [7/12 (58.3%) complete remission and 4/12 (33.3%) partial remission], while 1 patient did not respond to therapy. Twelve months after therapy, 68.8% (p = 0.003) of cases had achieved partial and 28.4% complete remission. Measurements of lymphocyte subpopulations did not reveal any changes except for the B cell depletion. B cell infiltrates captured per mm(3) of renal tissue in the diagnostic biopsy did not correlate with subsequent response. CONCLUSION: Depletion of B cells in idiopathic MGN was well tolerated and resulted in significant and long-lasting response rates in a series of 12 patients.