Adult-onset Minimal Change Nephrotic Syndrome Research Articles

Clinical and histopathological features related to time to complete remission in adult-onset minimal change nephrotic syndrome patients with corticosteroid treatment.

Minimal change nephrotic syndrome (MCNS) is a common type of nephrotic syndrome in adults, though evidence regarding its clinical and histopathological features related to time to complete remission (CR) is limited. This was a retrospective study of biopsy-proven, first-onset, adult MCNS patients who achieved CR after undergoing corticosteroid treatment. Body weight (BW) change rate was calculated as follows: (BW at admission - BW at discharge)/BW at discharge × 100. Histopathological examinations were performed, with particular attention given to tubulointerstitial lesions. Fifty-seven patients (median 41years old, range 22-63years; 37 males) were diagnosed with MCNS from 2007 to 2020. Time to CR was a median 11 (8-21) days. In addition to serum creatinine and urinary protein, BW change rate also showed a positive correlation with time to CR (rs = 0.438, p < 0.001; rs = 0.280, p = 0.035; rs = 0.544, p < 0.001; respectively), while multivariate Cox proportional hazards models also revealed those factors as significant predictors for longer time to CR. In MCNS patients with a higher BW change rate (n = 28), serum creatinine, urinary protein, histopathological score, and time to CR were significantly greater as compared to those with a lower BW change rate (n =29). Also, in those patients, histopathological interstitial edema was significantly associated with longer time to CR after adjustments for serum creatinine and urinary protein. The present results indicate that BW change rate can predict time to CR in adult-onset MCNS patients. Histopathologically, interstitial edema is also an important factor for time to CR in MCNS patients with greater BW increase.

Clinical and histopathological features of acute kidney injury in adult-onset minimal change nephrotic syndrome.

Acute kidney injury (AKI) is a common complication of minimal change nephrotic syndrome (MCNS), particularly in adults. To predict development of AKI, as defined by the Kidney Disease Improving Global Outcomes classification, we investigated clinical and histopathological features of adult-onset MCNS patients. A retrospective study was conducted with biopsy-proven adult-onset MCNS patients treated with corticosteroids. A total of 58 MCNS patients [49 (24-71) years old, 38 males] were diagnosed using kidney biopsy findings from 2005 to 2018 at Osaka City University Hospital, of whom 24 (41.4%) were found to be complicated with AKI. Age, urinary protein, increased body weight (difference from admission to discharge), and histopathological scores were significantly greater in patients with as compared to without AKI, while urinary protein, increased body weight, and interstitial edema score were significantly associated with AKI development [OR 1.55 (95% CI 1.04-2.31), 1.37 (95% CI 1.03-1.81), 20.7 (95% CI 1.76-243), respectively]. Of the 24 MCNS patients with AKI, 10 underwent transient hemodialysis treatment. Although histopathological features were not different, the time interval between disease onset and kidney biopsy was significantly longer for MCNS patients complicated with AKI requiring hemodialysis as compared to those for whom that was not required [32 (24-46) vs. 13 (10-23) days, p = 0.034]. These results indicate that urinary protein, increased body weight, and interstitial edema score are important information for predicting development of AKI in adult-onset MCNS patients.

Spontaneous remission of adult-onset minimal change nephrotic syndrome associated with influenza B infection: a case report

BackgroundWhile the majority of adult-onset minimal change nephrotic syndrome (MCNS) is a primary or an idiopathic form of disease, it can also occur as a secondary form. Reports on the spontaneous remission of MCNS are rare since the condition is typically treated with corticosteroids. We herein describe the spontaneous remission of adult-onset MCNS in a patient who developed nephrotic syndrome after type B influenza infection.Case presentationA 50-year-old woman experienced fever, cough, malaise, and low back pain, which had persisted for 6 days before she presented to our hospital, and edema of the face and limbs, which had persisted for 5 days before her presentation. She was diagnosed with type B influenza infection and later exhibited an exacerbation of facial edema, decreased urine output, and a high level of proteinuria. She was referred to our department after the diagnosis of nephrotic syndrome. On admission, her proteinuria level was 20.88 g/gCr and her selectivity index value was 0.13. The examination of a kidney biopsy specimen obtained on the fourth day of hospitalization under a light microscope revealed minor abnormalities. An immunofluorescence showed only nonspecific granular IgM deposits in the mesangium. Electron microscopy showed extensive foot process effacement without any immune complex deposits. Based on these findings, the patient was diagnosed with MCNS. After admission, the proteinuria decreased to 0.06 g/gCr with rest and sodium restriction (6 g/day) alone; a complete remission from nephrotic syndrome was observed at approximately 2 weeks after the onset of symptoms. There have been no signs of recurrence of nephrotic syndrome in the one years since.ConclusionWe experienced a rare case in which spontaneous remission of MCNS occurred within a short period of 2 weeks after influenza B infection. When patients present with nephrotic syndrome after an infection, it is necessary to consider MCNS in the differential diagnosis, which also includes post-infectious glomerulonephritis and the acute exacerbation of IgA nephropathy.

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

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. Case series. 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. Partial and complete remission, treatment resistance, relapse, complications, renal survival. 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. Retrospective design, variable treatment protocols. 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.

Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic Syndrome.

Glucocorticoid treatment is the first choice therapy for adults with minimal change nephrotic syndrome; however, this therapy associates with many adverse effects. Tacrolimus may be an alternative to conventional glucocorticoid therapy. To investigate this possibility, we conducted a prospective, randomized, controlled trial (WHO International Clinical Trials Registry Platform: ChiCTR-TRC-11001454) in eight renal units across China. We randomized enrolled patients with adult-onset minimal change nephrotic syndrome (n=119) to receive glucocorticoid therapy or tacrolimus after intravenous methylprednisolone (0.8 mg/kg per day) for 10 days. Patients received a conventional glucocorticoid regimen or tacrolimus monotherapy, starting with 0.05 mg/kg per day (target trough whole-blood level of 4-8 ng/ml) for 16-20 weeks and subsequently tapering over approximately 18 weeks. Remission occurred in 51 of 53 (96.2%; all complete remission) glucocorticoid-treated patients and 55 of 56 (98.3%; 52 complete and three partial remission) tacrolimus-treated patients (P=0.61 for remission; P=0.68 for complete remission). The groups had similar mean time to remission (P=0.55). Relapse occurred in 49.0% and 45.5% of the glucocorticoid- and tacrolimus-treated patients, respectively (P=0.71), with similar time to relapse (P=0.86). Seven (13.7%) glucocorticoid-treated and four (7.3%) tacrolimus-treated patients suffered frequent relapse (P=0.28); five glucocorticoid-treated and two tacrolimus-treated patients became drug dependent (P=0.26). Adverse events occurred more frequently in the glucocorticoid group (128 versus 81 in the tacrolimus group). Seven adverse events in the glucocorticoid group and two adverse events in the tacrolimus group were serious. Consequently, tacrolimus monotherapy after short-term intravenous methylprednisolone is noninferior to conventional glucocorticoid treatment for adult-onset minimal change nephrotic syndrome in this cohort.

Tacrolimus as rescue therapy for adult-onset refractory minimal change nephrotic syndrome with reversible acute renal failure

Some adult patients with minimal change nephrotic syndrome (MCNS) who are refractory to steroid treatment or combination with immunosuppressive drug developed reversible acute renal failure (ARF) due to persistent severe hypoalbuminemia and proteinuria. It is a challenge to find rescue therapies that are effective and safe in treating such difficult patients. In this prospective observational study, 13 patients with adult-onset MCNS, all unresponsive to treatment with a steroid or a steroid with other immunosuppressive drugs, were studied from January 2005 to February 2009. All patients developed ARF before enrollment. Oral tacrolimus (TAC) was started at 1 mg/day (target trough levels of 3-6 ng/mL) before serum creatinine (SCr) decreased to ≤133 μmol/L, and then increased doses were given (target trough level of 5-10 ng/mL) when SCr decreased to ≤133 μmol/L. Primary outcome variables were remission, and recovery from ARF. Secondary outcome variables were time to recovery from ARF, time to remission, relapse rate, changes in SCr and estimated glomerular filtration rate (eGFR). One patient discontinued TAC due to deterioration of ARF, and 12 patients recovered from ARF. The mean time to recovery from ARF was 15.8 ± 4.4 days. Nine patients (69.2%) experienced complete remission (CR) and two patients (15.4%) experienced partial remission (PR). The mean time to PR and CR was 4.8 ± 2.7 and 9.4 ± 2.3 weeks, respectively. After a mean follow-up of 69.6 months, 36.4% (4/11) of patients who had remission experienced relapses. One patient who was resistant to TAC therapy had a doubling of serum creatinine concentration during follow-up. TAC may be a suitable therapeutic option for treatment of adult-onset refractory MCNS with reversible ARF.

Comparison of the effects of intravenous methylprednisolone pulse versus oral prednisolone therapies on the first attack of minimal‐change nephrotic syndrome in adults

Minimal-change nephrotic syndrome (MCNS) is characterized by a good response to corticosteroid, but a high incidence of relapse. We compared the effect of intravenous methylprednisolone pulse plus oral prednisolone therapy (pulse group) with that of conventional oral prednisolone alone therapy (oral group) on the responsiveness and relapse in the first attack of adult-onset MCNS patients. Eighty-one adult patients with biopsy-proven MCNS, who were previously untreated and admitted to our hospital with their first attack of nephrotic syndrome, were analyzed retrospectively. They were arbitrarily assigned to either pulse group (n = 29, 1000 mg of methylprednisolone intravenously for 3 days, and then oral prednisolone 30 to 40 mg daily for 4 to 8 weeks) or oral group (n = 52, oral prednisolone 1 mg/kg daily for 4 to 8 weeks). We compared the time to response and relapse between the two groups. Time to steroid response was significantly shorter in the pulse group compared with the oral group (15.2 ± 10.2 vs 26.7 ± 17.6 days, P = 0.03). In 74 patients who reached remission within 12 weeks (pulse vs oral groups; 86.2% vs 96.2%, ns), the time to relapse was not different between two groups but the relapse rate was significantly higher in the pulse group (pulse vs oral groups; 60% vs 35%, P = 0.038). Kaplan-Meier analyses revealed that both complete remission rates within 4 weeks of the initial steroid therapy and relapse rate within 12 months after attaining remission were significantly higher in the pulse group than the oral group. In the Cox regression model, intravenous methylprednisolone pulse therapy had a significant effect on relapse (hazard ratio, 2.39 (95% confidence interval 1.11-5.15), P = 0.026). Intravenous methylprednisolone pulse followed by oral prednisolone therapy shows an earlier responsiveness but a much more frequent relapse compared with conventional oral prednisolone alone therapy for the first attack of adult-onset MCNS.

The characteristics of relapse in adult-onset minimal-change nephrotic syndrome

Although minimal-change nephrotic syndrome (MCNS) is highly steroid-responsive, the frequency of relapses in some patients is high, necessitating the administration of repeated courses of prednisolone in high doses. It is, therefore, necessary to identify factors that can predict this increased risk of relapse in some patients in order to establish useful treatment methods to reduce the risk. To clarify the factors that might increase the risk of relapses, the data of 82 Japanese adult patients with MCNS receiving treatment at our department were analyzed retrospectively. Of the total, 55 patients (67.1%) experienced relapse after showing an initial response. We divided the patients into two groups; namely, the nonrelapse group (n = 27) and the relapse group (n = 55), and compared the clinico-pathophysiological characteristics between the two groups. Significantly increased serum immunoglobulin E (IgE) levels (P = 0.0002) and increased frequency of steroid side effects were observed in the relapse group as compared to the nonrelapse group. To develop effective therapeutic modalities, it is important to have a thorough understanding of the clinico-pathophysiological characteristics of MCNS patients showing relapse.

Use of tacrolimus in steroid- and cyclophosphamide-resistant minimal change nephrotic syndrome

The authors report a case of adult-onset minimal change nephrotic syndrome (MCNS) that was resistant to steroid and cyclophosphamide therapy. Introduction of cyclosporin induced an usual cutaneous reaction of severe flushing attacks. Tacrolimus successfully alleviated both the nephrotic syndrome and the cutaneous side effect associated with cyclosporin use. The antiproteinuric mechanisms of tacrolimus and its potential in treating refractory MCNS and other forms of primary glomerulonephritides are discussed.

Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome.

To clarify factors influencing the response to corticosteroids and subsequent relapses, 62 Japanese adult patients with minimal change nephrotic syndrome were analyzed retrospectively. Five patients experienced remission spontaneously. Fifty-three patients entered complete remission, 3 patients entered partial remission, and 1 patient showed no response to corticosteroids. Fifty-three patients with complete remission were divided into two groups: 38 early responders who experienced remission completely within 8 weeks after starting treatment and 15 late responders who experienced remission after 8 weeks. Blood urea nitrogen and serum creatinine levels and proteinuria selectivity index at presentation were significantly worse in late than early responders. Relative interstitial volume determined by the point-counting method was significantly greater in late than early responders. Relative interstitial volume showed significant correlations with blood urea nitrogen, serum creatinine, and proteinuria selectivity index values. Thirty-three patients experienced a relapse; 13 patients experienced multiple relapses. Fifty-three patients with remission were divided into three groups: 16 patients who experienced relapse within 6 months after the initial response (early relapsers), 17 patients who experienced relapse after 6 months (late relapsers), and 20 patients who did not experience relapse (nonrelapsers). Mean age at onset was younger in early relapsers than late or nonrelapsers. Age at onset correlated inversely with relapse rate in 53 patients with remission and correlated positively with timing of the first relapse in 33 relapsers. It thus was suggested that impaired renal function and poor selectivity of proteinuria, which might be related to interstitial edema, were factors influencing a slower response to corticosteroids. Younger patients had a greater incidence of relapse and were prone to experience relapse earlier.

Minimal Change Nephrotic Syndrome in Adults: Response to Corticosteroid Therapy and Frequency of Relapse

Rate of response to a corticosteroid and frequency of relapse were studied in 33 patients with adult-onset minimal change nephrotic syndrome (MCNS). Of these, 28 patients were treated with oral prednisolone (PSL) at 1 mg/kg/d for from 4 to 8 weeks depending on their response, followed by PSL, at gradually tapering doses for 1 year. Five severely nephrotic patients received 1 g of methylprednisolone intravenously (IV) for 3 days, followed by 40 mg/d oral PSL for 4 to 8 weeks and finally PSL in gradually reduced doses. Sixteen patients (48%) were free of proteinuria within 4 weeks, and 25 (76%) within 8 weeks. Two patients required cyclophosphamide for induction of remission. Age at presentation was not significantly correlated with response time to corticosteroid therapy. Thirty-two (97%) went into remission, and relapse occurred in 11 (34%) of these. As assessed by the life-table method, 84% of patients were still in remission at 6 months after induction of remission, 75% after 1 year, and 63% during the follow-up period (mean, 47.1 +/- 29.1 months; range, 6 to 123 months). Incidence of relapse was not correlated with remission induction time, ie, earlier (less than or equal to 4 weeks) or later (greater than 4 weeks), but was greater in younger (less than 30 years of age) patients than older (greater than or equal to 30 years) patients (P less than 0.03). At the last follow-up, 31 patients (94%) were in complete remission and had normal renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult–onset minimal change nephrotic syndrome: A long–term follow–up

A series of 89 adult-onset nephrotic patients with minimal changes on renal biopsy was analyzed to compare the rate of response to corticosteroids and cytotoxic agents and the stability of remission or frequency of relapses at different ages. Severe hypertension and diminished renal function were more common in patients aged over 60 years, who formed 22.5% of the group. Seventy-five patients were given a first course of prednisolone in an initial dose of 60 mg/24 hr. After an eight week course of tapering doses of corticosteroids, only 45 of the 75 patients were in complete remission, 55 patients after 16 weeks and eventually 58 lost their proteinuria. The respective estimates of remission were 60%, 76% and 81%. Subsequently, of the 58 treated patients who responded, 24% never relapsed. Fifty-six percent of the patients relapsed on a single occasion or infrequently, and only 21% were frequent relapsers. Cyclophosphamide was used in 36 patients, in two as initial treatment, in 11 because of corticosteroid resistance, and in the remainder because of relapses. The time-course of loss of proteinuria was similar to that following treatment with corticosteroids, 25 (69%) losing proteinuria within 16 weeks. Only four patients failed to lose their nephrotic syndrome. Two of them had presented in acute renal failure and all four were over 60 years of age. The stability of remission after cyclophosphamide was better than that reported for children, only 13 of 36 showing relapses and 66% being in remission at five years, after which no further relapses were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of HLA-DRw8 and DQw3 with minimal change nephrotic syndrome in Japanese adults

The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.