Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine.

We report on the development of minimal change disease (MCD) with nephrotic syndrome and acute kidney injury (AKI), shortly after first injection of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 50-year-old previously healthy man was admitted to our hospital following the appearance of peripheral edema. Ten days earlier, he had received the first injection of the vaccine. Four days after injection, he developed lower leg edema, which rapidly progressed to anasarca. On admission, serum creatinine was 2.31 mg/dL and 24-hour urinary protein excretion was 6.9 grams. As kidney function continued to decline over the next days, empirical treatment was initiated with prednisone 80 mg/d. A kidney biopsy was performed and the findings were consistent with MCD. Ten days later, kidney function began to improve, gradually returning to normal. The clinical triad of MCD, nephrotic syndrome, and AKI has been previously described under a variety of circumstances, but not following the Pfizer-BioNTech COVID-19 vaccine. The association between the vaccination and MCD is at this time temporal and by exclusion, and by no means firmly established. We await further reports of similar cases to evaluate the true incidence of this possible vaccine side effect.

[Secondary glomerulonephritis in neurofibromatosis type 1. Two case reports]. / Síndrome nefrótico secundario en neurofibromatosis tipo 1. A propósito de dos casos.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder with systemic clinical manifestations. There are few publications about the renal effects of this disease, with renal vascular disease and adrenal tumors being the most frequent forms of renal involvement, while cases describing glomerular effects are exceptional. Despite the lack of published information, common molecular mechanisms in both NF-1 and nephrotic syndrome, involving the mTOR pathway, were suggested to explain a possible association between both pathologies. We present two cases of renal involvement in the form of nephrotic syndrome in patients diagnosed with NF1. A 41-year-old female was diagnosed of NF-1 in the context of a nephrotic syndrome with resistance to steroid treatment; the renal biopsy revealed a diagnosis of minimal changes disease. The second case is other 71-year-old woman with a history of NF-1, who presented a nephrotic syndrome and secondary renal amyloidosis.

Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Disease Activity in Adult-Onset Minimal Change Disease.

BACKGROUND: Cell adhesion molecules have been documented to be elevated in numerous immune inflammatory diseases. Minimal change disease (MCD) is an immune disorder. This study aimed to evaluate whether levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) reflect disease activity in adult-onset MCD. METHODS: A sandwich enzyme-linked immunosorbent assay was used to measure the soluble adhesion molecules in 40 patients with nephrotic-range proteinuria and biopsy-proven MCD, obtained at the time of diagnosis and during remission. Thirty-five age- and sex-matched healthy volunteers served as controls. RESULTS: Patients with MCD during the active stage showed significantly higher levels of sVCAM-1 and sE-selectin when compared to controls. Moreover, sVCAM-1 had significantly positive correlations with both urine protein and serum cholesterol, and was negatively associated with serum albumin. Multiple analyses showed that serum albumin was an independent predictor of sVCAM-1. The correlations between sE-selectin and other clinical parameters were not statistically significant. At follow-up, these markers systematically decreased as the disease went into remission, but the increase in sVCAM-1 persisted even in patients obtaining complete remission for 6 months. CONCLUSIONS: Patients with active MCD had increased levels of sVCAM-1 and sE-selectin. The correlation between sVCAM-1 and proteinuria, serum albumin and cholesterol and its decline during remission indicate that sVCAM-1 is associated with disease activity.

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study.

BACKGROUND: In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up. METHODS: Twenty males and 13 females with median of age 35 years (min-max: 3-76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed. RESULTS: In GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P = 0.004 and P = 0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P = 0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P = 0.038), tubular atrophy (P = 0.011) and globally sclerotic glomeruli (P = 0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P = 0.024 and P = 0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P = 0.010 and P < 0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P = 0.009), being lower in patients with negative than nuclear or dual dendrin expression (P = 0.034 and P = 0.004, respectively). CONCLUSION: In this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

Treatment patterns and steroid dose for adult minimal change disease relapses: A retrospective cohort study.

BACKGROUND: In patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment. METHODS: This retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to ≥10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course. RESULTS: During a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42-2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58-1.16; P = 0.25). CONCLUSIONS: Among patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10-20 mg/day).

Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models.

Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear.Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury.Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes.Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.

Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment.

Globally sclerotic glomeruli (GSG) occur with both normal aging and kidney disease. However, it is unknown whether any GSG or only GSG exceeding that expected for age is clinically important. To evaluate this, we identified patients with a glomerulopathy that often presents with nephrotic syndrome (focal segmental glomerulosclerosis, membranous nephropathy, or minimal change disease) in the setting of the Nephrotic Syndrome Study Network (NEPTUNE), China-Digital Kidney Pathology (DiKiP), and the Southeast Minnesota cohorts. Age-based thresholds (95th percentile) for GSG based on normotensive living kidney donors were used to classify each patient into one of three groups; no GSG, GSG normal for age, or GSG abnormal for age. The risk of end-stage renal disease or a 40% decline in glomerular filtration rate during follow-up was then compared between groups. Among the 425 patients studied, 170 had no GSG, 107 had GSG normal for age, and 148 had GSG abnormal for age. Compared to those with no GSG, the risk of kidney disease progression with GSG normal for age was similar but was significantly higher with GSG abnormal for age. This increased risk with GSG abnormal for age remained significant after adjustment for interstitial fibrosis, arteriosclerosis, age, hypertension, diabetes, body mass index, glomerulopathy type, glomerular filtration rate, and proteinuria. Thus, in patients with glomerulopathy that often presents with nephrotic syndrome, global glomerulosclerosis is clinically important only if it exceeds that expected for age.

The Clinical Course of Minimal Change Nephrotic Syndrome With Onset in Adulthood or Late Adolescence: A Case Series.

BACKGROUND: Few studies have examined the treatment and outcome of adult-onset minimal change nephrotic syndrome (MCNS). We retrospectively studied 125 patients who had MCNS with onset in either adulthood or late adolescence. Presenting characteristics, duration of initial treatment and response to treatment, relapse patterns, complications, and long-term outcome were studied. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with new-onset nephrotic syndrome 16 years or older and a histologic diagnosis of MCNS in 1985 to 2011 were identified from pathology records of 10 participating centers. OUTCOMES: Partial and complete remission, treatment resistance, relapse, complications, renal survival. RESULTS: Corticosteroids were given as initial treatment in 105 (84%) patients. After 16 weeks of corticosteroid treatment, 92 (88%) of these patients had reached remission. Median time to remission was 4 (IQR, 2-7) weeks. 7 (6%) patients initially received cyclophosphamide with or without corticosteroids, and all attained remission after a median of 4 (IQR, 3-11) weeks. 13 (10%) patients reached remission without immunosuppressive treatment. One or more relapses were observed in 57 (54%) patients who received initial corticosteroid treatment. Second-line cyclophosphamide resulted in stable remission in 57% of patients with relapsing MCNS. Acute kidney injury was observed in 50 (40%) patients. Recovery of kidney function occurred almost without exception. Arterial or venous thrombosis occurred in 11 (9%) patients. At the last follow-up, 113 (90%) patients were in remission and had preserved kidney function. 3 patients with steroid-resistant MCNS progressed to end-stage renal disease, which was associated with focal segmental glomerulosclerosis lesions on repeat biopsy. LIMITATIONS: Retrospective design, variable treatment protocols. CONCLUSIONS: The large majority of patients who had MCNS with onset in adulthood or late adolescence were treated with corticosteroids and reached remission, but many had relapses. Cyclophosphamide resulted in stable remission in many patients with relapses. Significant morbidity was observed due to acute kidney injury and other complications. Progression to end-stage renal disease occurred in a few patients and was explained by focal segmental glomerulosclerosis.

Comparison between patients with IgA nephropathy with minimal change disease and patients with minimal change disease.

OBJECTIVE: To compare the clinicopathological characteristics, treatment response, and prognosis between patients with IgAN nephropathy with minimal change disease (MCD-IgAN) and patients with minimal change disease (MCD). METHODS: 77 patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgAN Registry and 77 patients with MCD followed up for ≥ 3 years were retrospectively reviewed. RESULTS: MCD-IgAN and MCD patients had similar clinical presentations, both were predominantly young males, the disease mainly manifested as nephrotic syndrome, and the patients rarely presented with microscopic hematuria. Compared with the MCD group, patients with MCD-IgAN had lower levels of baseline serum albumin (p < 0.01) and eGFR (p < 0.05), a higher level of urine n-acetylglucosaminidase (p < 0.01), higher proportion of mesangial hypercellularity (M1), and more severe acute tubulointerstitial lesions in renal pathology (p < 0.01, p < 0.01, respectively). After 8 weeks of corticosteroid therapy, no significant differences were observed in the rate of complete remission, partial remission, and no remission between MCDIgAN and MCD patients (88.3% vs. 90.9%, 10.4% vs. 5.2%, 1.3% vs. 3.9%, p > 0.05). The median time to achieve remission was 4 weeks (range 1 - 24 weeks) and 4 weeks (range 1 - 28 weeks), respectively. No significant difference existed in the efficacy of corticosteroid between the two groups. During 3.96 years (range 3.0 - 8.5 years) of follow-up, no patients in the two groups entered end-stage renal disease (ESRD), only 2 patients (2.6%) with MCD-IgAN had > 50% reduction of eGFR. CONCLUSIONS: MCD-IgAN may be controlled well achieving a comparable clinical outcome as MCD but more frequently necessitates additional immunosuppressive medication.

Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease.

AIM: Treatment of frequently relapsing or steroid-dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long-term efficacy and safety are still limited. METHODS: We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid-dependent, biopsy-proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re-treatment. Biochemical and clinical parameters were monitored over an extended follow-up period of up to 43 months. RESULTS: Median steroid-free survival after RTX was 25 months (range 4-34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow-up period. CONCLUSIONS: Rituximab therapy is effective at maintaining prolonged steroid-free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid-dependent MCD.

Influence of acute kidney injury on the time to complete remission in adult minimal change nephrotic syndrome: a single-centre study.

AIM: Acute kidney injury (AKI) is a common complication of minimal change nephrotic syndrome (MCNS), particularly in adults. We evaluated the prevalence of AKI at the onset of adult MCNS and analyzed the influence of AKI on the duration of achieving complete remission (CR). METHODS: A retrospective, single-centre, dynamic cohort study was conducted with biopsy-proven, first-onset, adult MCNS patients treated with corticosteroids. Fifty-three consecutive patients diagnosed with MCNS from January 2000 to April 2014 were enrolled. Age, gender, daily urinary protein excretion, and serum creatinine levels were measured. To evaluate AKI during induction, we used the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI and judged AKI stage according to the fluctuations in serum creatinine levels during the first 4 weeks of starting corticosteroid therapy. RESULTS: Twenty patients (37.7%) met the AKI criteria and all 53 patients achieved CR within 1 year. Kaplan-Meier analysis showed that the median time to CR was significantly longer in patients with AKI than in patients without AKI. Cox proportional hazard analysis showed that the hazard ratio (HR) associated with the presence of AKI for achieving CR within 4 weeks was 0.36 after adjustment for age, gender, serum albumin, daily urinary protein excretion, hypertension, administration of 25% albumin, and methylprednisolone pulse therapy. A graded association was also observed between AKI stage and HR for achieving CR. CONCLUSIONS: The prevalence of AKI is high in adult patients with MCNS during induction therapy. AKI is an independent factor that delays the time to CR.

Regulatory T cells and minimal change nephropathy: in the midst of a complex network.

Minimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs ) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)-Ig fusion molecules inhibiting CD80 and/or with blockers of CD40-CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.

Síndrome nefrótico idiopático: recomendaciones de la Rama de Nefrología de la Sociedad Chilena de Pediatría. Parte 2 / Idiopathic Nephrotic Syndrome: recommendations of the Nephrology Branch of the Chilean Society of Pediatrics. Part two

El síndrome nefrótico idiopático es la glomerulopatía más frecuente en la infancia, afecta a 1-3/100 mil niños menores de 16 años y se presenta con más frecuencia entre los 2 y 10 años. Su causa es desconocida, y la mayoría de las veces responde a corticoides, con buen pronóstico a largo plazo. El síndrome nefrótico corticorresistente representa un 10-20% de los síndromes nefróticos idiopáticos en pediatría. Tiene mal pronóstico, y su manejo constituye un desafío terapéutico significativo. La mitad de los pacientes evoluciona a insuficiencia renal crónica terminal en un plazo de 5 años, estando expuestos además a las complicaciones secundarias a un síndrome nefrótico persistente y a efectos adversos de la terapia inmunosupresora. El objetivo fundamental del tratamiento es conseguir una remisión completa, pero una remisión parcial se asocia a una mejor sobrevida renal que la falta de respuesta. Este documento surgió de un esfuerzo colaborativo de la Rama de Nefrología de la Sociedad Chilena de Pediatría con el objetivo de ayudar a los pediatras y nefrólogos infantiles en el tratamiento del síndrome nefrótico idiopático en pediatría. En esta segunda parte, se discute el manejo del síndrome nefrótico corticorresistente, así como de las terapias no específicas.

Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown, and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. Steroid-resistant nephrotic syndrome represents 10-20% of idiopathic nephrotic syndrome in pediatrics. It has a poor prognosis, and its management is a significant therapeutic challenge. Half of patients evolve to end-stage renal disease within 5 years, and are additionally exposed to complications secondary to persistent NS and to the adverse effects of immunosuppressive therapy. The primary goal of treatment is to achieve complete remission, but even a partial remission is associated with a better renal survival than the lack of response. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric idiopathic nephrotic syndrome. In this second part, handling of steroid-resistant nephrotic syndrome as well as nonspecific therapies are discussed.

Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report.

The rate of hepatitis B virus (HBV) infection is high in the Chinese population, and the implications of HBV infection are widely recognized, and membranous nephropathy is the most common renal lesion to be associated with HBV infection. Minimal change disease (MCD) is one of the most important histopathological characteristics in patients with nephrotic syndrome. There is no any study to report that HBV infection is associated with the etiology of MCD. Herein, we report four MCD patients with HBV infection and speculate that there is an association of HBV infection with the pathological type of MCD. In this study, we also reported the treatment schedule for these four MCD patients, and found that the anti-virus alone and combination of anti-virus with immunosuppressive agent could obtain a benefit for MCD patients with HBV infection. However, a well-designed study should be performed to confirm this association.

Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults.

BACKGROUND: Cyclosporine and prednisolone combination therapy has been used in the treatment of minimal change nephrotic syndrome (MCNS). However, few studies have evaluated the efficacy of cyclosporine combined with intravenous methylprednisolone pulse therapy (MPT) as a first-line treatment for new-onset MCNS. We conducted a retrospective clinical study to evaluate the efficacy and safety of cyclosporine combined with MPT and oral prednisolone for new-onset MCNS in adults. METHODS: Forty-six adult patients with biopsy-proven MCNS were analyzed retrospectively. This study included three groups. Group 1 (n = 17) was treated with intravenous MPT (0.5 or 1.0 g/day for 3 days) followed by oral cyclosporine (2-3 mg/kg/day) and prednisolone (30 mg/day). Group 2 (n = 15) was treated with intravenous MPT followed by oral prednisolone (0.4-0.8 mg/kg/day). Group 3 (n = 14) was treated with oral prednisolone (0.6-1.0 mg/kg/day) alone. RESULTS: The length of hospital stay was the shortest in Group 1 (P < 0.001). The mean duration to achieve <20 mg/day of prednisolone was also the shortest in Group 1 (P < 0.05). Complete remission rates were 100 % in Group 1, 85.7 % in Group 2, and 69.2 % in Group 3 during the 9-month follow-up (P = 0.073). The rate of adverse effects caused by prednisolone was less in Group 1 (P < 0.05). Multivariate analysis revealed that the independent determinants of durations of remission were the selectivity index (P = 0.004), eGFR (P = 0.001) and the use of cyclosporine (P = 0.045). CONCLUSIONS: Combination therapy with cyclosporine may be a beneficial treatment option for new-onset MCNS in adults because of its clinical efficacy and safety.

Comparison of characteristics of chronic kidney diseases between Tibet plateau and plain areas.

BACKGROUND: The purpose of the current study was to investigate the pathological characteristics of chronic kidney diseases in the Tibet plateau and the plain. METHODS: 77 cases from the Tibet plateau and 154 cases from the plain of renal biopsied patients with chronic kidney diseases were compared in a randomized, and parallel controlled manner. Pathological characteristics were defined according to the standards of WHO and associated classifications. RESULTS: The ration of sex was shown that most of patients in the plateau region were female, whereas those in the plain were male. The characteristics of pathological types were shown that the patients in the plateau region were primarily minimal change disease, but IgA nephropathy was rare; meanwhile, the proportional lupus nephritis (LN) ratio of the secondary glomerulonephritis in the plateau region was significantly lower than those in the plain region. CONCLUSIONS: The current data demonstrated that the most common kidney disease in the Tibet Plateau region is still the primary glomerulonephritis as the same as those in the plain region. However, the primary glomerular disease in the plateau region is minimal change disease, and the most common clinical manifestations are the nephrotic syndrome. The IgA nephropathy in the plain is the most frequent disease. In terms of the secondary renal diseases, Henoch-Schnolein purpura nephritis are dominated in the plateau region, whereas LN-based diseases are frequently found in the plain. There is a statistical significance existed between those two groups.

Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin-lightening cream.

A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.

Ultrastructural changes of podocyte foot processes during the remission phase of minimal change disease of human kidney.

AIM: The current study was designed to observe the ultrastructural changes of podocyte foot processes during the remission phase and its relationship with the amount of the proteinuria in patients with minimal change disease (MCD). METHODS: Electron micrographs of glomerular capillaries were taken from 33 adult cases with MCD, including 12 cases with nephrotic syndrome, 15 cases in partial remission and six cases in complete remission. The foot processes were classified into three grades by the ratio of the height to basal width: 0.5-1, 1-2 and ≥2. The foot process width (FPW) and the number of foot processes in different grades per 10 µm of glomerular basement membrane (GBM) were measured. Normal renal tissues from 12 nephrectomies for renal carcinoma were selected as controls. RESULTS: There were statistical differences (P = 0.001) in the mean FPW among the nephrotic group (1566.4 ± 429.4 nm), partial remission group (1007.8 ± 234.9 nm), complete remission group (949.8 ± 168.2 nm) and normal controls (471.9 ± 51.8 nm). For the height-to-width ratio ≥2, the number of foot process per 10 µm GBM was significantly greater in the normal group than that in the complete remission group (0.84 ± 0.24 vs. 3.84 ± 1.80, P = 0.016). Taking all three groups of patients together, the mean FPW showed correlation with the level of proteinuria (r = 0.506, P = 0.003). CONCLUSION: There may be no causal relationship between proteinuria and foot process effacement. In complete remission phase, both FPW and shape of foot process had not returned to normal while proteinuria disappeared.

Unexplained severe acute kidney injury with rapid recovery of kidney function 11 months later after the start of high-dose steroid therapy.

Our patient appears to represent a previously unrecognized variant of steroid-responsive minimal change disease (MCD)/focal and segmental glomerulosclerosis (FSGS) in which severe AKI developed even though the serum albumin was essentially normal and proteinuria was minimal. This would be a paradox because the AKI of MCD/FSGS is a manifestation of severe nephrotic syndrome. To explain this paradox, it is suggested that our patient is a rare variant of a phenomenon that is well documented in steroid-responsive MCD/FSGS, specifically, glomerular permeability to large molecules is increased (accounting for the proteinuria) but decreased to small molecules (accounting for the low glomerular filtration rate). Our patient promptly recovered kidney function on steroid therapy even though he had been oliguric and dialysis dependent for nearly 11 months. The possible pathophysiologic mechanisms for this remarkable presentation and outcome are discussed.

Urine podocyte mRNAs, proteinuria, and progression in human glomerular diseases.

Model systems demonstrate that progression to ESRD is driven by progressive podocyte depletion (the podocyte depletion hypothesis) and can be noninvasively monitored through measurement of urine pellet podocyte mRNAs. To test these concepts in humans, we analyzed urine pellet mRNAs from 358 adult and pediatric kidney clinic patients and 291 controls (n=1143 samples). Compared with controls, urine podocyte mRNAs increased 79-fold (P<0.001) in patients with biopsy-proven glomerular disease and a 50% decrease in kidney function or progression to ESRD. An independent cohort of patients with Alport syndrome had a 23-fold increase in urinary podocyte mRNAs (P<0.001 compared with controls). Urinary podocyte mRNAs increased during active disease but returned to baseline on disease remission. Furthermore, urine podocyte mRNAs increased in all categories of glomerular disease evaluated, but levels ranged from high to normal, consistent with individual patient variability in the risk for progression. In contrast, urine podocyte mRNAs did not increase in polycystic kidney disease. The association between proteinuria and podocyturia varied markedly by glomerular disease type: a high correlation in minimal-change disease and a low correlation in membranous nephropathy. These data support the podocyte depletion hypothesis as the mechanism driving progression in all human glomerular diseases, suggest that urine pellet podocyte mRNAs could be useful for monitoring risk for progression and response to treatment, and provide novel insights into glomerular disease pathophysiology.