Cases Of Focal Segmental Glomerulosclerosis Research Articles

Focal segmental glomerulosclerosis in children complicated by posterior reversible encephalopathy syndrome

An uncommon side effect of cyclosporine A (CsA) use is posterior reversible encephalopathy syndrome (PRES). PRES usually develops because of disturbed capacity of posterior cerebral blood flow to autoregulate an acute rise in blood pressure. We present the case of a 10-year-old girl who was previously diagnosed in our department with focal segmental glomerulosclerosis. She was treated with CsA and developed seizures, progressive loss of consciousness, and visual disturbance on the 7th day of treatment. Brain magnetic resonance imaging showed degeneration of white matter with diffuse demyelination in the parietal and posterior occipital lobes, consistent with the diagnosis of PRES. Cases of PRES reported in children are usually secondary to immunosuppressive therapy in oncological and haematological diseases. Our case is the fifth reported case of focal segmental glomerulosclerosis in children treated with CsA and complicated by PRES. Rapid recognition of PRES and stopping neurotoxic therapy early are essential for a good prognosis.

A case of focal segmental glomerulosclerosis inferred by bevacizumab

A case of focal segmental glomerulosclerosis inferred by bevacizumab

A Successful Kidney Transplant for a Case of LMX1B Gene Mutation with a Positive Family History of Polycystic Kidney Disease

Nail-Patella syndrome is pleiotropic autosomal dominant disorder characterized by skeletal abnormalities and frequently renal disease. In this case report genetic analysis revealed a pathogenic heterozygous missense mutation of the LMX1B gene as c.[737G>A], p.([Arg246Gln)]. This variant is predicted to cause substitution of a basic arginine residue for a polar uncharged glutamine residue at position 246. The nucleotide at position 737 and amino acid at position 246 are both highly conserved across species. Although LMX1B mutation causing hereditary focal segmental glomerulosclerosis (FSGS) without any extra-renal involvement has been described as nail patella like renal disease (NPLRD) where there is partial impairment of transcriptional activity with these mutations leading to absence of other features of nail patella syndrome (NPS). Our case report gets interesting as patient had progressed relatively quickly to end stage renal disease. Some of heterozygous gene mutation FSGS cases are expected to recur after kidney transplantation. Our case has received a successful renal transplant from brother which is working well for the last 3 years without any evidence of recurrence. Another interesting feature of our case was the strong family history of unrelated other renal genetic disorder autosomal dominant adult polycystic kidney disease (ADPKD).

Correlation analysis of renal ultrasound elastography and clinical and pathological changes in patients with chronic kidney disease .

To analyze the correlations of renal tissue elastography with clinical biochemical indicators and pathological changes in patients with chronic kidney disease (CKD) as well as to explore the potential for renal tissue elastography as a new, noninvasive method for the dynamic monitoring of renal disease progression, efficacy assessment, and prognosis evaluation. Patients admitted to the Department of Nephrology of the First Affiliated Hospital of China Medical University from August 2014 to January 2015 who had undergone renal biopsies were selected. A total of 113 patients with CKD and 16 healthy controls were enrolled in this study, including 61 males and 52 females. In total, 23 cases of IgA nephropathy, 39 cases of membranous nephropathy, 15 cases of minimal-change nephropathy (MCN), and 7 cases of focal segmental glomerulosclerosis were included. The Young's moduli (YM) of the renal cortex and medulla were measured using an AixPlorer Doppler ultrasound with full digital color from Supersonic Imagine. The correlations between the YM of renal tissue and clinical biochemical indicators of blood and urine and the differences in Young's moduli among the different pathological changes in the patients with CKD were analyzed. The YM of the CKD patients was significantly higher than that of the control group (p<0.05), and the YM of the renal cortex and medulla gradually increased with the progression of CKD. The YM of the renal cortex in the stage-G5 CKD patients was significantly higher than that of the CKD patients in stages G1 - G3 (p<0.05). The YM of the renal medulla of the CKD patients in stages G3-5 was significantly higher than that of the CKD patients in stages G1-G2. On univariate analysis, the YM of the renal cortex was correlated with systolic blood pressure, serum creatinine, cystatin C, serum albumin, serum phosphorus, calcium and phosphorus products, uric acid, iPTH, urinary N-acetyl-glucosaminidase (NAG), eGFR, and hemoglobin levels. And the YM of the renal medulla was correlated with systolic blood pressure, serum creatinine, serum albumin, uric acid, iPTH, urinary microalbumin (MA), urinary NAG, and hemoglobin levels. On multivariate analysis, serum cystatin C (β=0.485, p=0.018) and uric acid (β=0.418, p=0.039) levels were independently correlated with the YM of the renal cortex, while serum creatinine (β=0.380, p=0.019) and uric acid (β=0.482, p=0.004) levels, as well as smoking (β=0.337, p=0.009), were independently correlated with the YM of the renal medulla. The YMs of the renal cortex in patients with membranous nephropathy and IgA nephropathy were significantly higher than those in the patients with CN (p<0.05). The YM of the renal cortices of the patients in phases IV and V of IgA nephropathy based on the Lee grading system were significantly higher than those of the patients in phases II and III (p<0.05). According to the Oxford classification for IgA nephropathy, the Young's moduli of the renal cortex and medulla in T1 and T2 patients were significantly higher than those in T0 patients (p<0.05). The YM of the renal cortex and medulla showed no statistically-significant differences among the different stages of membranous nephropathy. The YM of the renal cortex and medulla are associated with the progression of renal insufficiency, and renal ultrasound elastography shows promise as a new means of assessing the stage of CKD. Renal ultrasound elastography is expected to become a new, noninvasive method for the early diagnosis of CKD and the dynamic monitoring of disease progression as well as the assessment of efficacy and prognosis. .

Focal segmental glomerulosclerosis associated with mitochondrial disease

Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases caused by mutations in either the mitochondrial or nuclear DNA. Glomerular diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS) associated with a new tRNA mutation site. A 34-year-old man with a history of living related kidney transplantation, diabetes, hearing loss, and developmental delay presented to the outpatient clinic with complaints of new behavioral difficulties, worsening symptoms, and brain involvement on imaging. Physical examination was remarkable for difficulty hearing, a pattern of dysarthric speech, and cerebellar gait. Laboratory investigations including lactate levels were unremarkable. Based on this set of clinical circumstances, concern for an underlying genetic abnormality was raised. Multiple metabolic tests were unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change at position m.5538G>A. Genotype-phenotype correlations are consistent with this tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is the first case describing FSGS-associated MD caused by an m.5538 G>A mutation. Consideration of an underlying MD should be made in patients presenting with deafness, neurologic changes, diabetes, and renal failure.

Collapsing glomerulopathy is common in the setting of thrombotic microangiopathy of the native kidney

Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 patients withhistologically proven TMA in the native kidney, with special emphasis on changes due to focal segmental glomerulosclerosis (FSGS). Histological TMA was related tohypertensive nephropathy in 21 patients, genetic complement abnormalities in 9, drugs in 7, and to other causes in 16 patients. Almost half (26 patients) presented with arteriolar, 6 with glomerular, and 21 with mixed TMA. Using the Columbia classification system for the 53 patients with histological TMA, 33 had concurrent FSGS lesions with collapsing glomerulopathy the dominant variant in 19 patients (58% of the FSGS cases), not otherwise specified in 9 patients, cellular in 3, and perihilar or tip lesions in 1 patient each. The presence of FSGS was associated with a poor renal prognosis, with no prognostic difference between collapsing glomerulopathy and other FSGS variants. Thus, collapsing glomerulopathy is frequently found in native kidney biopsies with TMA, suggesting that endothelial injury may play an important role in the pathophysiology of FSGS.

Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old Japanese woman: a case report and review of the literature.

Focal segmental glomerulosclerosis (FSGS) is classified into five variants, with the collapsing variant being the most rare. Collapsing FSGS is characterized by a black racial predominance and is often associated with human immunodeficiency virus-associated nephropathy. However, the number of idiopathic cases is increasing and the presentation of non-black patients becoming more routine. Our analysis of 15 previous reports investigating FSGS variants shows that the collapsing variant accounts for 10.6% of FSGS cases and its average age of onset is 32years old. The current case is one of the oldest cases of idiopathic collapsing FSGS identified, being an 81-year-old Japanese woman. She presented with severe renal insufficiency (serum creatinine 7.9mg/dL, albumin 1.5g/dL) and so underwent hemodialysis immediately. Urinalysis demonstrated 3+ proteinuria and 3+ hematuria and the serological work up was all negative. Renal biopsy showed wrinkling of capillary walls with collapse lumens in every glomerulus, without endothelial tubuloreticular inclusions. Combined treatment with steroids, cyclosporine and low-density lipoprotein apheresis increased urine output slightly but she was unable to withdraw from hemodialysis and died 3months later. This variant is reported to have the highest rate of progression to end-stage renal disease, regardless of the therapeutic intervention. However, there are also examples of cases with partial or complete remission in the literature. Progressive cases, like the current case, seem to be difficult to induce remission in, so it is important to diagnose idiopathic collapsing FSGS at an early stage by performing a renal biopsy, even in elderly patients.

A prospective study of collapsing focal segmental glomerulosclerosis

Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar.

Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy.

Background:Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman’s capsule in IgAN cases with mild glomerular histologic change. Methods:To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. Results:In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. Conclusions:Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes.

A Rare Case of Focal Segmental Glomerulosclerosis in a Patient with Grade a Benign Thymoma: A Case Report and Review of the Literature

Thymoma is a rare mediastinal tumour that is often (40%) accompanied by different paraneoplastic syndromes and glomerulonephritis is one of the recognized entities. Minimal change disease is the most common paraneoplastic glomerulonephritis associated with thymoma, followed by membranous nephropathy, focal segmental glomerulosclerosis, rapidly proliferative glomerulonephritis and lupus nephritis. Literature review illustrates that most of the thymoma associated nephropathy cases were reported in association with more malignant thymic tumors like WHO grade B and C tumours. Herein we report a rare case of focal segmental glomerulosclerosis in a patient with grade A benign thymoma, a combination which has never been reported previously. She had poor response to corticosteroids and died due to neutropenic sepsis following azathioprine therapy.

Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children.

Focal segmental glomerulosclerosis (FSGS) is a nephrotic syndrome. Up to around 80% of cases of primary FSGS are resistant to steroid treatment. A large proportion of patients with steroid-resistant FSGS progress to end-stage renal disease. The purpose of treatment is to obtain a complete remission of proteinuria, a necessary step that precedes improved renal survival and reduces the risk of progression to chronic kidney disease. When this is not possible, the secondary goal is a partial remission of proteinuria. Reduction or remission of proteinuria is the most important factor predictive of renal survival. We will review the current updated strategies for treatment of primary FSGS in children, including traditional therapies consisting of corticosteroids and calcineurin inhibitors and novel therapies such as rituximab, abatacept, adalimumab, and fresolimumab.

Interferon Induced Focal Segmental Glomerulosclerosis.

Behçet's disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS) is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet's disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

α-Actinin-4 Gene Mutations, Steroid Responsiveness and FSGS in Adult Onset-Nephrotic Syndrome

Focal segmental glomerulosclerosis (FSGS) is a common pattern of injury seen in primary as well as secondary renal disorders and is a major cause of steroid- resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). SRNS is defined by resistance to standard steroid therapy and it remains one of the most intractable causes of kidney failure. Mutations in α-actinin-4 gene (ACTN4) represent a frequent cause of SRNS associated with an adult onset form of FSGS. We screened a cohort of 374 subjects from the South Indian population for the presence of two missense mutations, K255E and S262P in exon 8 of ACTN4 gene encoding α-actinin-4, an actinfilament crosslinking and bundling protein. Our results revealed that these two mutations were seen only among the patients (4%) in heterozygous form and absent in the controls suggesting that, these mutations were found to be disease causing in nature and the regulation of the actin cytoskeleton of glomerular podocytes may be altered in the patients. Further categorization revealed that K255E and S262P mutations were together responsible for 5% of SRNS and 15% of FSGS cases in our study group. Conversely, these mutations were not found in the controls as well as in the patients with steroid–sensitive nephrotic syndrome (SSNS). This is the first report from India, more studies are warranted to establish the frequency of ACTN4 mutations in our population and such analysis may help in developing mutation(s) specific therapeutic interventions in future.

P3-24: Secondary hypertension in a tunisian internal medicine department

Secondary hypertension (SH) refers to arterial hypertension due to an identifiable and often curable cause. It affects approximately 5-10% of the general hypertensive population. SH can be caused by conditions that affect kidneys, arteries, heart or endocrine system. Our aim is to describe the different causes of SH noted in our patients. It is a retrospective study of 240 patients followed for a SH at the Internal Medicine Department of the Tunisian Military Hospital from 2000 to 2015. The diagnosis of SH in these patients was suspected in front of clinical and biological arguments and confirmed by the further explorations guiding a suitable therapeutic attitude. Renal causes were the main etiology of SH (233 patients) with acute glomerular nephritis (AGN) in 4 cases, primary chronic glomerular nephropathy (CGN) in 14 cases, including 8 cases of membranous glomerulonephritis, 2 cases of focal segmental glomerulosclerosis and 4 cases of membrano-proliferative glomerulonephritis. Secondary CGN were dominated by diabetic nephropathy in 174 cases, lupus nephropathy in 10 cases and rheumatoid purpura in one case. Congenital kidney diseases were represented by hereditary polycystic kidney disease in 20 patients and Alport syndrome in 2 patients. The renovascular hypertension was noted in 8 cases. The endocrine causes were present in 6 patients (2 cases of Conn syndrome, 2 cases of hyperthyroidism, 1 case of bilateral adrenal hyperplasia and another case of pheochromocytoma). One patient had SH with a cardiac cause that was aortic coarctation. The prevalence of SH exceeds 30% among patients with resistant hypertension. Common causes include chronic kidney diseases, primary aldosteronism, renovascular hypertension and obstructive sleep apnea. In our study, renal parenchymal disease particularly diabetes is the most common cause of SH. Physicians should be judicious about evaluation of a potentially curable cause of hypertension. Careful clinical evaluation and simple algorithms help avoid unnecessary investigations. In patients with SH, early detection and treatment are important to minimize and prevent irreversible changes in the vasculature and target organs.

Focal and segmental glomerulosclerosis: clinical and kidney biopsy correlations.

BackgroundPrimary focal segmental glomerulosclerosis (FSGS) is a common glomerular disease in adults and ranks among the top causes of a primary glomerular disease causing end-stage renal disease (ESRD). Primary FSGS is, however, a diagnosis of exclusion and distinction between primary versus secondary FSGS is not always obvious, resulting in a number of patients with secondary FSGS undergoing unnecessary immunosuppressive therapy.MethodsWe reviewed the Mayo Clinic Renal Pathology Database for patients with a diagnosis of FSGS on native renal biopsy and divided the patients into nephrotic syndrome-associated (NS-associated) and non-nephrotic syndrome-associated (NNS-associated) FSGS as a first approximation followed by dividing the lesion according to the degree of foot process effacement (FPE) on electron microscopy (EM) examination.ResultsA total of 41 patients with FSGS with complete evaluation were identified. Of these, 18 were classified as having NS and 23 were classified as having NNS. Baseline characteristics (age, gender, body mass index, serum creatinine and hematuria) were not different between the groups. All of the patients with NS showed diffuse FPE ranging from 80 to 100% (mean 96%). On the other hand, of the 23 patients in the NNS group, 22 had segmental FPE and showed patchy effacement, with all cases showing 20–60% FPE (mean of 48%).ConclusionAdult patients presenting with NS, an FSGS lesion on LM, extensive FPE (≥80%) on EM examination and no risk factors associated with secondary FSGS are likely to have primary FSGS. Conversely, the absence of NS in a patient with segmental FPE on EM strongly suggests a secondary FSGS. Dividing FSGS into the presence or absence of NS together with the degree of FPE on EM examination is more helpful as it provides a more practical way to separate patients into cases of primary versus secondary FSGS.

The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis

The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found an inverse correlation between the estimated glomerular filtration rate (eGFR) and suPAR. As patients with FSGS present at different eGFRs, we studied the relationship between eGFR and suPAR in a cohort of 476 non-FSGS patients and 54 patients with biopsy-proven idiopathic FSGS. In the non-FSGS patients, eGFR was the strongest significant determinant of suPAR. The proposed cutoff for suPAR in FSGS patients was exceeded in 17%, 39%, and 88% in patients with eGFRs of more than 60, 45-60, and 30-45 ml/min per 1.73 m(2), respectively. In patients with eGFR of <30 ml/min per 1.73 m(2), suPAR exceeded the cutoff in 95% of patients. Levels of suPAR in patients with idiopathic FSGS overlapped with non-FSGS controls and for any given eGFR did not discriminate FSGS cases from non-FSGS controls. In the overall cohort, there was a negative association between idiopathic FSGS and suPAR, and idiopathic FSGS was not an independent predictor of FSGS concentration over 3000 pg/ml. Thus, this study does not support an absolute, eGFR-independent, suPAR concentration cutoff as a biomarker for underlying FSGS pathology and questions the validity of relative, eGFR-dependent suPAR cutoff values.

Podocin and beta dystroglycan expression to study podocyte-podocyte and basement membrane matrix connections in adult protienuric states.

BackgroundPodocytes can be the primary site of injury or secondarily involved in various protienuric states. Cross talk between adjacent foot processes and with basement membrane is important for slit diaphragm function. Does expression of podocyte associated proteins in kidney biopsies alter with site/type of primary injury? Genetic mutations of podocin result in steroid resistant FSGS. Can protein expression of podocin predict resistant cases to initiate further genetic evaluation?MethodsAdult patients (n-88) with protienuria- minimal change disease(MCD)-22, focal segmental glomerulosclerosis(FSGS)-21,membranous glomerulonephritis(MGN)-25 and IgA nephropathy(IgAN)-20 were selected for immunohistochemistry with podocin and beta dystroglycan . Results were graded (0 - 3+scale )and compared with control biopsies and internal control. Treatment and follow up (6 months -2 ½ years) of FSGS and MCD cases were collected.ResultsThere was intense to moderate staining of the podocytes with podocin and β dystroglycan in the glomeruli in all cases (MCD, FSGS, IgAN and MGN) except for weak staining with β dystroglycan in 3 cases of MCD. There was loss of immunostains in areas of segmental/global sclerosis. There was no significant difference in the staining pattern between the groups. In primary podocytopathies, staining pattern did not differ between steroid resistant, sensitive or dependent cases.ConclusionsImmunohistochemical expression of podocin and β dystroglycan does not differ in nephropathies which have different site of injury depending on absence (MCD and FSGS) or presence of immune deposits and their localization (MGN and IgAN). Podocin and β dystroglycan staining did not differentiate steroid sensitive and resistant cases, hence, does not give clue to initiate genetic studies. However, analysis of bigger cohort may be required.SummaryPodocin and β dystroglycan immunohistochemistry was done to analyze podocyte - podocyte and podocyte -basement membrane matrix connections in adult protienuric states. Primary podocytopathies i.e. MCD and FSGS and secondary podocytopathy due to immune complex deposition i.e. MGN (subepithelial) and IgAN (mesangial) were analyzed. There was no difference in staining patterns between primary and secondary podocytopathies or between steroid sensitive, resistant and dependent cases of FSGS and MCD.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2258608781052786

Cyclosporine A for the treatment of refractory nephrotic syndrome with renal dysfunction

Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30–40 ml/min/1.73 m2, and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all patients as represented by the improvement in the eGFR (28.6±3.8 ml/min/1.73 m2 prior to treatment versus 99.3±21.9 ml/min/1.73 m2 6 months subsequent to treatment). Few adverse CsA-related events were observed. These results suggest that renal dysfunction is not an absolute contraindication for CsA treatment in patients with RNS. The use of CsA is safe and efficacious and may, in certain cases, improve renal function in patients with RNS and renal impairment.

Urine But Not Serum Soluble Urokinase Receptor (suPAR) May Identify Cases of Recurrent FSGS in Kidney Transplant Candidates

Recently, serum soluble urokinase receptor (suPAR) has been proposed as a cause of two thirds of cases of focal segmental glomerulosclerosis (FSGS). It was noted to be uniquely elevated in cases of primary FSGS, with higher levels noted in cases that recurred after transplantation. It is also suggested as a possible target and marker of therapy. We studied serum and urine suPAR from pretransplantation banked samples from 86 well-characterized kidney transplant recipients and 10 healthy controls to determine its prognostic utility. Causes of native kidney disease were primary FSGS, diabetic nephropathy, membranous nephropathy, immunoglobulin A nephropathy, and autosomal dominant polycystic kidney disease. suPAR was measured using a commercially available enzyme-linked immunosorbent assay kit. Urinary suPAR was indexed to creatinine. Both serum and urine suPAR correlated with proteinuria and albuminuria. Serum suPAR was found to be elevated in all transplant candidates with advanced renal disease compared with healthy controls and could not differentiate disease diagnosis. Urine suPAR was elevated in cases of recurrent FSGS compared with all other causes of end-stage renal disease. Recurrent FSGS cases had substantially higher proteinuria compared with all other cases. However, elevated urinary suPAR showed a trend in providing additional prognostic information beyond proteinuria in the small cohort of recurrent FSGS cases. In advanced renal disease, elevated serum suPAR is not unique to FSGS cases. Urinary suPAR appears to be higher in cases of FSGS destined for recurrence and merits further evaluation.