Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

BackgroundCollapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear.Methods and ResultsPatient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection. Two weeks post infection, his serum creatinine (SCr) increased to 2.01 mg/dL from a baseline of 1.40 mg/dL, and he developed concomitant nephrotic range proteinuria. The first renal transplant biopsy showed FSGS. Four weeks later, his sCr level increased to 2.65 mg/dL with worsening proteinuria, and a second renal transplant biopsy revealed CGN. Patient #2 was a 32-year-old African American man whose native renal biopsy revealed primary FSGS. He received a renal transplant with initial post-transplant sCr level at 1.17 mg/dL. Four months later, his sCr and protein-to-creatinine ratio began to rise. Sequential biopsies revealed that the patient had developed recurrent FSGS, which progressed to show features of CGN. The CGN was further confirmed in his transplant kidney graft at autopsy later.ConclusionsThis is the first case report of CGN in a white renal recipient with COVID-19 infection. The pathologic presentations of FSGS progressing to collapsing FSGS in our 2 renal transplant recipients suggest that FSGS and GGN may share a common pathophysiologic mechanism of podocytopathy.     

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.S. Scientific Renal Transplant Registry between the years 1988-97, we found 19259 adult primary renal transplant recipients, of which 2414 patients had FSGS as their primary diagnosis as compared to 16845 patients who had other types of glomerulonephritis (GN). A Cox proportional hazard model was used to estimate death-censored graft survival among FSGS patients with a zero mismatch LRD kidney transplant. The model included a triple interaction term comparing FSGS vs. GN vs. living donation (LD) vs. cadaveric donation (CAD) vs. zero mismatch (six antigen or HLA-identical) vs. mismatch. Annually adjusted death censored graft loss rates per 1000 patients (ADGL) were calculated. Focal segmental glomerulosclerosis patients receiving a zero mismatch LRD kidney transplant had the lowest ADGL rate, losing 10.5 grafts per 1000 patients per year. Not significantly different but higher (14.3) was the ADGL rate for LD, zero mismatch GN recipients. The ADGL rate was significantly higher in FSGS recipients who received a LD, mismatched transplant (36.5). Focal segmental glomerulosclerosis patients who received a CAD, zero mismatched graft (44.1), or CAD, mismatched graft (63.2), had significantly higher ADGL rates. Zero mismatch LRD kidney transplants are not a risk factor for graft loss in FSGS patients but are associated with significantly better death-censored graft survival as compared to CAD 6-antigen match or mismatched donations.     

Long-Term Outcomes of Kidney Transplant Recipients With Primary Idiopathic Focal Segmental Glomerulosclerosis

Background

Few data exist on recurrence rates, treatment response, and long-term outcomes in kidney transplant recipients (KTR) with primary focal segmental glomerulosclerosis (FSGS).

Strumpell's Disease in a Family with Hereditary Focal Segmental Glomerulosclerosis

Strumpell's familial spastic paraplegia is a rare hereditary disease, clinically characterized by progressive disturbance of gait. Focal Segmental Glomerulosclerosis (FSGS) is a frequent glomerulopathy, with an extremely rare familial subtype. The cases of two brothers with Strumpell's disease are reported, who also developed glomerular renal disease, most probably familial FSGS. The genetics of the two disorders, Strumpell's paraplegia and familial FSGS, are discussed, together with the possibility of a parallel transmission.     

Cardiovascular Disease in Early Kidney Transplantation: Comparison Between Living and Deceased Donor Recipients

BackgroundCardiovascular disease (CVD) mortality is extremely high among kidney transplant recipients (KTRs), particularly in the first months after transplantation. Few data are available comparing the cardiovascular profile between KTRs from living versus deceased donors.Objectives and methodsThe aim of the present study was to evaluate the prevalence of CVD in the first 2 months following transplantation, among 120 KTRs of living versus deceased donor organs.ResultsLeft ventricular hypertrophy was observed in 65% of patients, coronary artery calcification in 30%, and cardiac arrhythmias in 46%. CVD was more prevalent among KTRs from deceased versus living donors: ventricular hypertrophy 87% versus 59% (P = .008); coronary artery calcification 42% versus 24% (P = .04); and cardiac arrhythmias 59% versus 39% (P = .06). Multiple logistic regression analysis adjusted for age and dialysis vintage, showed graft donor to not be associated with the prevalence of any CVD (β coefficient 0.912, 95% confidence interval 0.276–3.012, P = .88).ConclusionIn conclusion, the present study demonstrated an elevated prevalence of CVD among KTRs. Patient characteristics, mainly longer length on dialysis seemed to contribute to a greater prevalence of cardiovascular complications among KTRs from deceased compared with living donors on univariate but not multivariate analysis.     

原发性局灶节段性肾小球硬化症(FSGS)治疗进展

原发性局灶节段性肾小球硬化症FSGS是临床上常见的慢性肾脏疾病.肾病综合征(FSGS)可表现为尿蛋白的流失,血浆白蛋白降低、水肿、血脂紊乱等.而大量蛋白尿、血清肌酐升高是其进展为肾功能衰竭的非常重要的危险因素,一旦肾病综合征未能缓解,则50%的患者在今后4年内肌酐翻倍,6～8年之后即发展为肾功能衰竭.尤其对于难治性肾病综合征(FSGS),治疗疗效欠佳、病变反复复发,预后较差,目前临床上尚无明确的有效治疗方案.由于FSGS病理生理学上包含了各种不同的肾小球损伤,非单一病变;而多发的病因,基因和环境因素影响的不同等,都增加了其治疗难度,个体间治疗效果亦存在较大差异[1].而随着各种新型免疫抑制药物如雨后春笋般诞生,相信对于激素依赖或抵抗的患者可有效的减少尿蛋白的流失,改善肾功能及预后.     

Intensive and Prolonged Treatment of Focal and Segmental Glomerulosclerosis Recurrence in Adult Kidney Transplant Recipients: A Pilot Study

No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 ± 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05–0.3 g/day) and 0.19 g/day (range 0.05–1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.     

Focal Segmental Glomerulosclerosis in a Patient with Large Bilateral Asymptomatic Adrenal Myelolipomas

Adrenal myelolipomas are rare benign tumors, usually discovered by chance in patients with hypertension, obesity or various endocrine disorders. Focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. So far, no association between the two conditions has been described. We report a case of a woman admitted for nephrotic syndrome, in which a coexistence of FSGS and bilateral large adrenal myelolipomas was revealed.     

Transplantation With APOL1 Risk Variant Kidney May Be Associated With Lifetime Risk for Recurrence of Focal Segmental Glomerulosclerosis: A Case Report and Review of Literature

The APOL1 gene mutation is increasingly recognized as an import factor in living kidney donation. APOL1 gene variants prevalent in the African American population have been associated with increased risk of glomerulopathy. Shorter allograft survival is seen in transplants from donors who had 2 risk APOL1 gene alleles. In the early posttransplant period, kidneys with 2 risk alleles of APOL1 had higher risk of graft loss compared to 1 or 0 risk alleles, but by year 4 of transplant it was almost similar. The authors have suggested that recipients of kidney transplants with 2 risk alleles may only be at risk for kidney failure during the early initial period. We present here a case of a patient with 2 risk APOL1 alleles who received renal transplant from her identical twin and developed glomerulopathy 18 years after the transplant. No case of APOL1-associated recurrent glomerulonephritis has been described in a recipient after 10 years. This suggests that the risk of recurrence of glomerulopathy in allograft transplants with 2 risk allele variants may not be limited to the initial post-transplant period; rather, it may be a lifetime risk.     

原发性局灶节段性肾小球硬化的中西医结合个体化治疗的疗效观察

目的 :研究中西医结合个体化治疗原发性局灶节段性肾小球硬化 (pFSGS)的疗效。方法 :对 30例经肾活检术确诊为 pFSGS的患者根据不同个体采用中西医结合个体化治疗方案 ,供选择药物有 :强的松 (Pred)、雷公藤多甙片 (T1)、血管紧张素转换酶抑制剂 (ACEI)、环磷酰胺 (CTX)、非甾体类消炎药 (NsAID)、益肾通络方 (黄芪、首乌、金樱子、积雪草、桃仁、制军 )等。以 15例未按上述正规治疗的患者作对照。结果 :治疗观察 (33.5 8± 2 0 .6 7)月 ,治疗组完全缓解 16例 (5 3.33% ) ,显效 8例 (2 6 .6 7% ) ,有效 5例 (16 .6 7% ) ,无效 1例 (3.33% ) ,其中 10例肾衰竭的患者 ,治后 8例恢复正常。对照组未见临床缓解或显效 ,仅 7例有效 ,差异显著 (P <0 .0 1)。结论 :中西医结合个体化治疗pFSGS的疗效明显优于对照组