Diffuse Foot Research Articles

Minimal Change Disease With Nephrotic Syndrome Associated With Coronavirus Disease 2019 After Apolipoprotein L1 Risk Variant Kidney Transplant: A Case Report

Kidney injury is a well-known complication in people with coronavirus disease 2019 (COVID-19). In kidney transplant recipients with COVID-19, presentation with nephrotic syndrome has not been well described. We report on a 49-year-old black female kidney transplant recipient who presented 25 years after transplant with clinical features of nephrotic syndrome following a diagnosis of COVID-19. Histologic examination showed acute tubular injury with unremarkable glomeruli on light microscopy and diffuse foot process effacement of podocytes on electron microscopy, consistent with minimal change–like podocyte injury. Apolipoprotein L1 (APOL1) genetic testing confirmed 2 high-risk APOL1 alleles in the kidney donor. We speculate that COVID-19–induced systemic or local cytokine release could serve as a second hit in the presence of APOL1 risk alleles and mediate a podocytopathy manifesting as nephrotic syndrome. The presented case with minimal change–like disease, occurring in the context of the donor high-risk APOL1 genotype, extends the spectrum of clinical manifestations in COVID-19–associated nephropathy.

Characterization of IgA Deposition in the Kidney of Patients with IgA Nephropathy and Minimal Change.

Approximately 5% of patients with IgA nephropathy (IgAN) exhibit mild mesangial lesions with acute onset nephrotic syndrome and diffuse foot process effacement representative of minimal change disease (MCD). It is not clear whether these unusual cases of IgAN with MCD (IgAN-MCD) are variant types of IgAN or coincidental deposition of IgA in patients with MCD. In a retrospective multicenter cohort study of 18 hospitals in Korea, we analyzed 46 patients with IgAN-MCD. Patients with endocapillary proliferation, segmental sclerosis, and crescent were excluded, and the clinical features and prognosis of IgAN-MCD were compared with those of pure MCD. In addition, we performed galactose-deficient IgA1 (KM55) staining to characterize IgAN-MCD. Among the 21,697 patients with glomerulonephritis enrolled in the database, 46 patients (0.21%) were diagnosed with IgAN-MCD, and 1610 patients (7.4%) with pure MCD. The 46 patients with IgAN-MCD accounted for 0.6% of primary IgAN patients (n = 7584). There was no difference in prognosis between patients with IgAN-MCD and those with only MCD. IgA and KM55 showed double positivity in all patients with IgAN-MCD (n = 4) or primary IgAN (n = 5) under double immunofluorescent staining. However, in four patients with lupus nephritis, mesangial IgA was deposited, but galactose-deficient-IgA1 (Gd-IgA1) was not. These findings suggest that IgAN-MCD is a dual glomerulopathy in which MCD was superimposed on possibly indolent IgAN. We confirmed by KM55 staining that IgAN-MCD is true IgAN, enabling better characterizations of the disease. Furthermore, IgAN-MCD shows a good prognosis when treated according to the usual MCD treatment modality.

Spectrum of podocytopathies in new-onset nephrotic syndrome following COVID-19 disease: a report of 2 cases

BackgroundCoronavirus disease-2019 (COVID-19) is an ongoing pandemic which has affected over 12 million people across the globe. Manifestations in different organs systems are being reported regularly. Renal biopsy findings in hospitalized COVID-19 patients presenting solely with acute kidney injury (AKI) have recently been described in published literature in few case reports. The findings include diffuse acute tubular injury (ATI) along with the glomerular lesion of collapsing glomerulopathy (CG). However, nephrotic syndrome as the presenting complaint of COVID-19 has not been reported widely, neither has any other glomerular lesion other than CG.Case presentationWe describe the kidney biopsy findings of two patients who had recent diagnoses of COVID-19 and presented with new-onset nephrotic syndrome. Renal biopsy in both patients showed ATI (as in previous reports) and distinct glomerular findings on light microscopy – that of minimal change disease (MCD) initially in one patient followed by CG in a subsequent biopsy and CG at the outset in the other patient. The electron microscopic findings in both patients were that of severe podocytopathy (diffuse and severe podocyte foot process effacement).ConclusionOur cases highlight a novel clinical presentation of COVID-19 renal disease, not described before, that of new-onset nephrotic syndrome. While all published case reports describe CG as the glomerular pathology, we describe a non-CG pathology (MCD) in one of our cases, thereby adding to the repertoire of renal pathology described in association with COVID-19 patients. However, the exact mechanism by which podocyte injury or podocytopathy occurs in all such cases is still unknown. Optimal treatment options for these patients also remains unknown at this time.

P0288CLINICOPATHOLOGICAL FEATURES OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS: STEPS FOR AN ACCURATE CLASSIFICATION - A SINGLE CENTRE CASE SERIES

Abstract Background and Aims Focal and segmental glomerulosclerosis (FSGS) is a histological pattern that is defined by the presence of segmental sclerosis of at least one glomerulus in the kidney biopsy. However, the etiological classification of this lesion remains challenging in clinical practice. FSGS can be divided into primary/idiopathic, genetic or secondary. Nowadays here is no biochemical marker that allows clinicians to distinguish between these categories nor a pathognomonic feature associated to a particular subtype of FSGS. Also, genetic testing is not suitable for all patients. Although it is crucial to determine the cause of FSGS, this is not easily done in clinical practice. Herein we present a series of patients with histologic diagnosis of FSGS in which clinical and histological criteria were applied in order to establish the etiologic classification of FSGS. Method A retrospective analysis of 359 patients who performed kidney biopsy from January 2010 to December 2018 was performed. Patients with histological features of FSGS were identified. Clinical, laboratorial and pathological data were collected, including treatment and outcome. Patients were classified as having genetic FSGS if they accomplished at least one of the following: a) nephrotic syndrome resistant to corticosteroids; b) non-nephrotic proteinuria or nephrotic syndrome with normal serum albumin; c) non-nephrotic proteinuria or nephrotic syndrome with focal foot process effacement or d) non-nephrotic proteinuria with diffuse foot process effacement. The remaining patients were classified as secondary FSGS (if they presented a disease known to be associated with FSGS) or primary FSGS. Each group was divided according to treatment with corticoid, other immunosuppressive agents or and RAAS blockage. Renal outcomes were assessed (progression to ESKD). Results A total of 359 kidney biopsies were performed between January 2010 to December 2018, 66 with a histological pattern of FSGS. 65% (N=43) were males, 71% (N=47) were Caucasian and 23% (N=15) were black. 74% (N=49) had past medical history of hypertension, 26% (N=17) diabetes mellitus and 5% (N=3) had HIV. The majority of patients were classified as having secondary FSGS (52%, N=34), 23% (N=15) were classified as primary and as 25% (N=17) genetic/idiopathic. From the genetic group 58.8% (N=10) were treated with corticoid, 12% (N=2) with other IS agents and 71% (N=12) with ACE/ARB. 29% (N=5) evolved to ESKD (median time to dialysis 11 IQR 1-30). In the primary FSGS group 40% (N=6) were treated with corticoid, 7% (N=1) with other IS agents and 80% (N=12) with ACE/ARB. 27% (N=4) evolved to ESKD (median time to dialysis 0 months, IQR 0-33). In the genetic group 59% (N=10) were treated with corticoid, 12% (N=2) with other IS agents and 71%(N=12) with ACE/ARB. 29% (N=5) evolved to ESKD (median time to dialysis 11 months, IQR 1-30). Conclusion FSGS is a very prevalent glomerular disease and its correct etiologic classification aids in better treatment choice. Although its etiology is not straightforward in most of the patients, some clinical and histological characteristics aid in FSGS classification.

P0427IGA GLOMERULONEPHRITIS WITH MASSIVE PROTEINURIA- CASE SERIES WITH CLINICAL AND PATHOHISTOLOGICAL REVIEW

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not common in IgAN. It is reported to occur in 5-10% of patients with IgAN. Clinical presentation with massive proteinuria is exceptional. Method We retrospectively analyzed patients with pathohistologically proven IgAN who initially presented with 24h proteinuria greater than 10 gr. Here we presented their clinical, biochemical and pathohistological (electron microscopy-EM, was provided in all cases) characteristics with clinical outcomes. Data were taken from Renal biopsy Registry of Department of Nephrology Dubrava University hospital. Results All together 12 patients (10 M, 2 F) average age 53 (range 25-81) years were included. This represents 3,2% of all IgAN patients in our Renal biopsy Registry (presently there are more than 2100 patients in total, 366 with IgAN). Arterial hypertension had 10 out of 12 patients and three patients had diabetes mellitus type 2. Other significant comorbidities included lung adenocarcinoma in one patient, history of preeclampsia, mitral valve replacement surgery and liver cirrhosis, each in one patient. Average serum creatinine level at presentation was 223,9 (90-549) µmol/L and average 24h proteinuria was 14,6 (10,2-32) gr. All patients had haematuria. Renal insufficiency was found in 7 patients and additionally in two patients rapidoprogressive clinical pattern was recognized. Oxford classification was applied for all patients. In all except one, mesangial hypercellularity (M1) was found, endocapillary proliferation (E1) in 4 and cellular crescents in 5 patients (C1 in 4, C2 in 1 patient). The average percentage of globally sclerosing glomeruli was 32% (10-85%) and IFTA was 33% (10-60%), respectively. On EM diffuse podocyte foot processes effacement was documented only in two patients. In patients with diabetes mellitus there were not signs of diabetic nephropathy (i.e. thickened GBM on EM). Two patients who presented with purpuric rash and arthritis were considered to have IgA vasculitis (Henoch Schoenlein purpura). Considering treatment, glucocorticosteroids and RAAS blockators (apart from those who were dialysis dependent) were introduced. Five patients were also treated with cyclophosphamide. Average time of follow-up was 53 months (2-156). Regarding clinical outcomes, 4 patients achieved remission (2 partial and 2 complete). One of those experienced clinical relaps and underwent kidney rebiosy. In one patient stationary course and in another one progression of renal insufficiency were noted. Both patients diagnosed as IgA vasculitis were dialysis depended at presentation and during follow-up period unfortunately died. Two more patients died latter on as a consequence of a non-renal disorders. One more patient who developed ESRD was transplanted but afterwards he rejected the graft. One patient was lost from follow-up. Conclusion Proteinuria is well known independent progression risk factor in IgAN. In presented study we showed that almost one third of IgAN patients who manifested with massive proteinuria ended up in ESRD in relatively short follow-up period.

SAT-429 CMV-ASSOCIATED CONGENITAL NEPHROTIC SYNDROME: CORRELATION OF CLINICAL, HISTOPATHOLOGICAL AND GENETIC FINDINGS

Congenital nephrotic syndrome (cNS), defined by onset during the first three months of life, is a rare clinical disorder with traditionally poor renal outcome. It is caused by homozygous or compound heterozygous mutations of a growing number of genes affecting podocyte and/or glomerular basement membrane integrity, with or without syndromic features. Other potential etiologies include antenatal or perinatal infections, or (other) systemic disorders. Case description and systematic review of the literature in PubMed using the key words "CMV", "congenital” or "infant", and "nephrotic” or "glomerulonephritis". This report describes an ex-preterm baby who had been referred at two weeks corrected gestational age for suspected surgical abdomen in view of progressive abdominal distention, scrotal edema and vomiting. The patient was found to have full-blown nephrotic syndrome with urine protein-to-creatinine ratio of > 6 g/g, hypoalbuminemia <10 g/L, hypercholesterolemia and anemia, and elevated liver transaminases. He had syndromic features. Diagnostic workup revealed an active CMV infection, based on CMV-specific IgM and positive CMV PCR from blood and urine. Routine pregnancy screen for intrauterine infections had been negative. Subsequent maternal diagnostic revealed high maternal anti-CMV IgG (IgM negative) and positive CMV PCR. The infant’s kidney biopsy showed focal mesangial proliferation and sclerosing glomerulonephritis with cellular or fibro-cellular crescents in less than 5% of glomeruli, while global or segmental sclerosis associated with older fibrous crescents was noted in 10% of glomeruli, in addition to interstitial fibrosis and tubular atrophy. Routine immune fluorescence was negative. Electron microscopy revealed diffuse podocyte foot process effacement, but no immune complexes or endothelial tubule-reticular inclusions. Infiltrating (interstitial) lymphocytes stained positive for CD3 and CD20, respectively. Results of the genetic mutation screen are pending. After 6 weeks of treatment with valganciclovir, the CMV PCR has become negative, but the infant continues to demonstrate severe proteinuria and hypoalbuminemia. Review of the available literature reveals an important overlap between cNS due to known monogenic causes and CMV infection. Although the number of defined cases in the literature is scarce, we noted divergent histopathological features in CMV-associated cNS, dependent on the presence or absence of cognate genetic mutations as shown in the Table. CMV is a rare cause of nephrotic syndrome presenting soon after birth. Screening for relevant mutations is essential since congenital infections can complicate or mask an underlying genetic etiology leading to the failure of CMV-directed antiviral therapy and poor renal outcome.

Lupus Podocytopathy: An Overview.

In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.

SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts.

We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin-binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development. We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli. Expression data from the Nephroseq database showed glomerular and nonglomerular SHROOM3 had opposing associations with renal function in CKD biopsy samples. In human allografts, homozygosity at rs17319721, the SHROOM3 locus linked with lower GFR, was associated with reduced albuminuria by 2 years after transplant. Although our previous data showed reduced renal fibrosis with tubular Shroom3 knockdown, this study found that glomerular but not tubular Shroom3 knockdown induced albuminuria. Electron microscopy revealed diffuse foot process effacement, and glomerular RNA-sequencing showed enrichment of tyrosine kinase signaling and podocyte actin cytoskeleton pathways in knockdown mice. Screening SHROOM3-interacting proteins identified FYN (a src-kinase) as a candidate.We confirmed the interaction of endogenous SHROOM3 with FYN in human podocytes via a critical Src homology 3-binding domain, distinct from its ROCK-binding domain. Shroom3-Fyn interaction was required in vitro and in vivo for activation of Fyn kinase and downstream nephrin phosphorylation in podocytes. SHROOM3 knockdown altered podocyte morphology, cytoskeleton, adhesion, and migration. We demonstrate a novel mechanism that may explain SHROOM3's dichotomous associations in glomerular versus nonglomerular compartments in CKD.

Minimal change disease associated with anti-PD1 immunotherapy: a case report

BackgroundOncologic immunotherapy is a form of therapy intended to reactivate the immune response to tumor cells using agents that modulate immune checkpoints, such as programmed cell death protein 1 and its ligand (PD-1/PD-L), and cytotoxic T-lymphocyte-associated antigen 4. Along with activation of the immune system to tumors, immune-mediated kidney side effects have been reported, most of which are cases of interstitial nephritis. Glomerular disease, however, appears rare.Case presentationHerein, we describe a patient with nephrotic syndrome related to treatment with an anti-PD1 antibody for Hodgkin lymphoma. Following the third dose of anti-PD1 antibody, the patient developed massive proteinuria and nephrotic syndrome. Kidney biopsy showed diffuse podocyte foot process effacement upon electron microscopy, which was consistent with minimal change disease. Corticosteroid treatment yielded full and rapid remission of nephrotic syndrome in 1 month.ConclusionThe present case suggests an association between anti-PD1 therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapy, patients should be routinely monitored for kidney side effects associated with these agents.

Soluble klotho as a marker of renal fibrosis and podocyte injuries in human kidneys.

Klotho deficiency is relevant to renal fibrosis and podocyte injury in vivo and in vitro. We examined whether histological findings of renal biopsy specimens were associated with the levels of soluble klotho in humans. We investigated renal biopsy specimens of 67 patients and detailed microscopic findings were reviewed. Soluble serum/urinary klotho and urinary angiotensinogen were assessed by enzyme-linked immunosorbent assays, and tissue klotho expression was assessed by immunohistochemical staining. The median age of the study participants was 35.6 years. High serum klotho levels (≥14 pg/mL) were associated with decreased odds ratios (ORs) of interstitial fibrosis (OR = 0.019, P = 0.003) and segmental sclerosis (OR = 0.190, P = 0.022) in multivariable logistic regression analysis. Patients with a lower urinary klotho-to-creatinine ratio (UKCR) were significantly more likely to have diffuse foot process effacement (OR = 0.450, P = 0.010). The area under the receiver-operating characteristic curve (AUC) of serum klotho for predicting interstitial fibrosis was 0.920 (95% CI, 0.844–0.996), and the best cut-off value of serum klotho was 138.1 pg/mL. The AUC of UKCR for predicting diffuse foot process effacement was 0.754 (95% CI, 0.636–0.872), and the best cut-off value of UKCR was 96.7 pg/mgCr. Urinary angiotensinogen-to-creatinine ratio was not associated with serum klotho, UKCR, or any pathological finding. Our data suggested that soluble serum and urinary klotho levels represent a potential biomarker to predict renal fibrosis and podocyte injury in humans.

A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products.

There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting.

Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy.

Altered activities of long noncoding RNAs (lncRNAs) have been implicated in the regulation of microRNAs. microRNA-27a (miR-27a) upregulation has been shown to induce endoplasmic reticulum (ER) stress podocyte injury in diabetic nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of miR-27a with long intergenic noncoding RNA 1619 (LINC01619) and the target gene. LINC01619 downregulation was found in human DN renal biopsy tissues and contributed to proteinuria and diminished renal function. LINC01619 was expressed in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619 exerted biological function by serving as a "sponge" for miR-27a, which negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In diabetic rats and high-glucose cultured podocytes, LINC01619 triggered oxidative stress and podocyte injuries as demonstrated by increased apoptosis, diffuse podocyte foot process effacement, and decreased renal function. Innovation and Conclusion: This study demonstrates that LINC01619 functions as a competing endogenous RNA and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury in DN. Antioxid. Redox Signal. 29, 355-376.

Recurrent focal segmental glomerulosclerosis after kidney transplant in adults: A report on various treatment regimens

Aim: Recurrence of focal segmental glomerulosclerosis (FSGS) in the post-transplant setting is variable with high rates of graft loss. Risk factors of recurrence include young age and Caucasian race. Data on outcome of recurrent FSGS from South Asia is scanty. We describe our experience of managing adults with recurrent FSGS with different therapies. Settings and Design: The study was conducted at the Department of Nephrology and Renal transplant surgery, Post Graduate Institute of Medical education and Research Institute, Chandigarh, India, and this was an observational study. Methods: We analyzed outcomes of patients with biopsy-proven recurrent FSGS over the last 5 years (2012–2017). Recurrence was defined as significant proteinuria (albuminuria ≥ 3+) and a demonstrable FSGS lesion on light microscopy and/or electron microscopy suggestive of diffuse foot process effacement. Results: Thirteen patients with 14 recurrences of FSGS post-renal transplant were identified. Mean age of the patients was 33.15 (±8.32) years. Median time to recurrence of FSGS was 45 days. Plasma exchange (PLEX) alone was used in two patients with 50% in remission. Combined PLEX and rituximab were used in six recurrences with remission in 83.3% of them. Five recurrences were treated with only angiotensin-converting enzyme inhibitor/angiotensin receptor blockade (ACEi/ARB) due to financial constraints. Of them, 4 (80%) achieved remission in proteinuria. One patient did not receive any therapy and expired in the 1st month of follow-up. Conclusion: The present series is one of the largest reports of recurrent FSGS from South Asia. Furthermore, the current report strengthens the use of ACEi/ARB in patients with recurrent FSGS.

Lupus podocytopathy: a distinct entity of lupus nephritis.

Systemic lupus erythematosus (SLE) patients clinically presenting with nephrotic syndrome demonstrating minimal change disease (MCD), mesangial proliferation (MsP) or focal segmental glomerulosclerosis (FSGS), while on electronic microscopy, diffuse podocyte foot process effacement in absence of sub-epithelial or sub-endothelial deposition is the only morphological feature and now diagnosed as lupus podocytopathy. Lupus podocytopathy with glomerular morphology of MCD or MsP usually presents with typical nephrotic syndrome and sensitive to glucocorticoid treatment, but the relapse rate could reach up to 90% on maintenance treatment with glucocorticoid alone. Glucocorticoid plus other immunosuppressive agents could significantly decrease the relapse rate. Lupus podocytopathy with FSGS presents with a higher rate of acute kidney injury and less sensitivity to glucocorticoid treatment. The long-term outcomes of lupus podocytopathy are optimistic, but pathological transition could occur after renal relapses. The unique clinical and morphological features of lupus podocytopathy indicate that this special SLE-associated glomerulopathy should be included in the upcoming revised pathological classification of lupus nephritis.

Nephrotic syndrome and acute kidney injury induced by malathion toxicity

We treated a case of acute kidney injury and nephrotic syndrome after malathion inhalation. A 69-year-old Japanese man presented with oedema 15 days after inhalation of malathion, a widely used...

Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis.

Cutaneous and systemic plasmacytosis (CSP) is a rare lymphoproliferative disorder that mainly affects middle-aged Asian individuals. Although Castleman disease is often complicated with various renal involvements, glomerulonephritis associated with CSP, which is considered as a variant of Castleman disease, is rare. This report presents the case of a 41-year-old Japanese man with nephrotic syndrome associated with CSP. Renal biopsy findings showed focal segmental glomerulosclerosis (FSGS) and diffusely mild segmental mesangial proliferation. Plasma cell infiltration in the interstitium was not observed. Electron microscopic findings showed diffuse foot process effacement, localized involvement of subendothelial space widening with amorphous materials, and endothelial cell swelling. Lymph node biopsy findings denied Castleman disease. His skin regions and proteinuria were successfully treated with prednisolone and cyclosporine. The causal relationship between CSP and FSGS is unknown. However, increased serum levels of IL-6 and VEGF and decreased VEGF expression in the podocyte may contribute to renal lesions in patients with CSP. To our best knowledge, this is the first case of a patient with FSGS associated with CSP.

Intravascular large B cell lymphoma limited in renal glomaruli: A case presented as nephrotic syndrome

Intravascular large B cell lymphoma (IVLBCL) is a rare type of non-Hodgkin lymphoma, characterized by selective proliferation of B cells within the lumens of small vessels. We report a case of IVLBCL with the invaded B cells limited in the lumen of glomerular capillary loops. The patient presented with nephrotic syndrome. Histological examination of renal biopsy specimens showed infiltration of neoplastic cells limited in glomerular capillary loops, accompanied by diffuse foot process effacement only in those capillary loops with the infiltrative cells. Immunohistochemistry shows that the infiltrative cells were positive for bcl-2, bcl-6, CD20, MUM1 and ki-67, consistent with atypical cells deriving from B cells. Unfortunately, the patient refused the further treatment and died soon after the diagnosis.

What are we missing in the clinical trials of focal segmental glomerulosclerosis?

Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain. The separation of primary from secondary FSGS clinically and pathologically is challenging, but full-blown nephrotic syndrome and diffuse (universal) foot process effacement are strong signals for a primary form of FSGS. It is imperative that clinical trials designed to investigate therapeutic strategies for patients with a lesion of FSGS pay careful attention to the separation of primary from secondary forms of FSGS. This critical review provides a rationale and a process for helping to ensure that this is accomplished, such that clinical trials provide useful information and treatment responsiveness applicable to the primary forms of FSGS.

Crystalline podocytopathy and tubulopathy without overt glomerular proteinuria in a patient with multiple myeloma

Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain–secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury.

Clinical-Morphological Features and Outcomes of Lupus Podocytopathy.

Lupus podocytopathy, which is characterized by diffuse foot process effacement without peripheral capillary wall immune deposits and glomerular proliferation, has been described in SLE patients with nephrotic syndrome in case reports and small series. This study aimed to better characterize the incidence, clinical-morphologic features, and outcomes of such patients from a large Chinese cohort. Lupus podocytopathy was identified from 3750 biopsies of SLE patients obtained from 2000 to 2013 that showed mild glomerular histology in patients with a clinical sign of nephrotic syndrome. The biopsy results were divided into three groups: glomerular minimal change, mesangial proliferation, and FSGS. Fifty (1.33%) cases were identified as lupus podocytopathy and included minimal change in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases. Extensive foot process effacement appeared in all the biopsies and mesangial electron-dense deposits were present in 47 biopsies. All patients demonstrated nephrotic syndrome, and the median proteinuria was 5.72 g/24 h (interquartile range [IQR], 3.82, 6.92). Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR, 2, 8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule-interstitial injury and a much lower complete remission rate. During follow-up of a median of 62 (IQR, 36, 84) months, renal relapses occurred in 28 (59.6%) patients. No patient died or developed ESRD. The findings from this cohort study suggest that lupus podocytopathy may represent a special entity of lupus nephritis with distinct clinical-morphologic features. The differences in AKI incidence, tubular injury severity, and response to treatment between the patients with minimal change/mesangial proliferation and those with FSGS patterns indicate two different subtypes of lupus podocytopathy.