Long-term Renal Prognosis Research Articles

Is autosomal dominant polycystic kidney disease an early sweet disease?

The clinical course of autosomal dominant polycystic kidney disease (ADPKD) starts in childhood. Evidence of the beneficial impact of early nephron-protective strategies and lifestyle modifications on ADPKD prognosis is accumulating. Recent studies have described the association of overweight and obesity with rapid disease progression in adults with ADPKD. Moreover, defective glucose metabolism and metabolic reprogramming have been reported in distinct ADPKD models highlighting these pathways as potential therapeutic targets in ADPKD. Several "metabolic" approaches are currently under evaluation in adults, including ketogenic diet, food restriction, and metformin therapy. No data are available on the impact of these approaches in childhood thus far. Yet, according to World Health Organization (WHO), we are currently facing a childhood obesity crisis with an increased prevalence of overweight/obesity in the pediatric population associated with a cardio-metabolic risk profile. The present review summarizes the knowledge about the role of glucose metabolism in the pathophysiology of ADPKD and underscores the possible harm of overweight and obesity in ADPKD especially in terms of long-term cardiovascular outcomes and renal prognosis.

Renal Ultrasonographic Abnormalities at Initial Presentation of Children Diagnosed with Acute Lymphoblastic Leukemia and Long-Term Renal Functions and Prognosis in Survivors.

ObjectivesThe kidney is a vulnerable organ for acute lymphoblastic leukemia (ALL), by the disease, and various associated clinical pictures. This retrospective study aims to document renal ultrasound abnormalities in children with newly diagnosed ALL as well as to investigate the correlation between renal findings and clinical/laboratory/survival data.MethodsAll children (age <18 years) with ALL were included in the study. An increase in size/nephromegaly (NM) or hyperechogenicity (HE) of the kidneys at first admission was accepted as a pathological renal abnormality. The clinical/laboratory findings, survival, and long-term renal functions were compared between patients with and without NM/HE.ResultsThe incidence of NM±HE was 12% in 163 patients. Enlargement of spleen, liver, or both and, hypercreatininemia was independently correlated with the presence of NM/HE. After the induction therapy, ultrasound findings were resolved in all patients, and NM/HE did not influence ALL prognosis. All survivors had normal renal functions in long term.ConclusionThe renal ultrasound abnormalities are not uncommon in children with leukemia at admission, without a negative impact on leukemia prognosis and on long-term renal functions.

Renal Prognosis in Children With Tubulointerstitial Nephritis and Uveitis Syndrome

IntroductionTubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome.MethodsWe performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018.ResultsA total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9–62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (−4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3–152.7) and <90 ml/min per 1.73 m2 in 20 patients.ConclusionIn our study, nearly half of the patients had renal sequelae at last follow-up. Given the possible progression to chronic kidney disease, long-term monitoring of children with TINU syndrome is mandatory. Approximately a quarter of the children had asymptomatic uveitis suggesting all children presenting with TIN should undergo systematic ophthalmologic screening even in the absence of ocular signs.

Increased risk of end-stage renal disease in patients with systemic sclerosis

Objective Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc. Method We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD. Results After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39–3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97–8.71) and the younger population (HR = 7.09, 95% CI 2.31–21.80). Conclusion There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.

Challenging Disease Ontology by Instances of Atypical PKHD1 and PKD1 Genetics.

BackgroundAutosomal polycystic kidney disease is distinguished into dominant (ADPKD) and recessive (ARPKD) inheritance usually caused by either monoallelic (PKD1/PKD2) or biallelic (PKHD1) germline variation. Clinical presentations are genotype-dependent ranging from fetal demise to mild chronic kidney disease (CKD) in adults. Additionally, exemptions from dominant and recessive inheritance have been reported in both disorders resulting in respective phenocopies. Here, we comparatively report three young adults with microcystic-hyperechogenic kidney morphology based on unexpected genetic alterations beyond typical inheritance.MethodsNext-generation sequencing (NGS)-based gene panel analysis and multiplex ligation-dependent probe amplification (MLPA) of PKD-associated genes, familial segregation analysis, and reverse phenotyping.ResultsThree unrelated individuals presented in late adolescence for differential diagnosis of incidental microcystic-hyperechogenic kidneys with preserved kidney and liver function. Upon genetic analysis, we identified a homozygous hypomorphic PKHD1 missense variant causing pseudodominant inheritance in a family, a large monoallelic PKDH1-deletion with atypical transmission, and biallelic PKD1 missense hypomorphs with recessive inheritance.ConclusionBy this report, we illustrate clinical presentations associated with atypical PKD-gene alterations beyond traditional modes of inheritance. Large monoallelic PKHD1-alterations as well as biallelic hypomorphs of both PKD1 and PKHD1 may lead to mild CKD in the absence of prominent macrocyst formation and functional liver impairment. The long-term renal prognosis throughout life, however, remains undetermined. Increased detection of atypical inheritance challenges our current thinking of disease ontology not only in PKD but also in Mendelian disorders in general.

MO125NON-AMYLOID TYPE OF MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: CLINICAL AND MORPHOLOGICAL SPECTRUM AND LONG-TERM RENAL OUTCOME*

Abstract Background and Aims Monoclonal gammopathy of renal significance (MGRS) is a clinically and morphologically diverse kidney damage caused by monoclonal immunoglobulin (IG) produced by a "small" B-cell clone. Non-amyloid type of MGRS is considered to be rare but associated with poor kidney outcome (KO). The analysis of the prevalence, clinical and morphological spectrum and long-term renal prognosis in different degrees of hematological response (HR) in patients with non-amyloid type of MGRS became the goal of this study. Method In this one-center prospective study performed from 01.01.2011 till 01.03.2020 patients with MGRS were enrolled. Criteria of MGRS were following: i) morphologically verified monoclonal IG related kidney damage and ii) an aberrant clone in the bone marrow and/or the level of serum/urine paraprotein not met the hematological criteria for treatment initiation. Cases of renal AL-amyloidosis were excluded. The morphological spectrum of non-amyloid MGRS, treatment, hematological and renal responses (RR) were analyzed. HR was assessed depending on the type of monoclonal IG according to the accepted criteria. The presence of RR was considered as a decrease in daily proteinuria&amp;gt; 30% from the initial level or less than 0.5 g in the absence of a decrease in eGFR&amp;gt; 25% at the time of the end of follow-up. The progression of renal dysfunction was documented with a decrease in eGFR&amp;gt; 25% from baseline. KO was determined as initiation of renal replacement therapy or eGFR &amp;lt;15 ml/min/1.73m2 at the end of follow-up. Long-term renal survival was assessed by the Kaplan-Meier method. The median follow-up period was 18 (4; 38) months. Results The prevalence of non-amyloid MGRS was 1.4% (n = 29) of all performed kidney biopsies (n = 2042). Clinical and demographic parameters of the group are presented in the figure 1. Serum or/and urine paraprotein was detected in 23 patients as κ (30.4%), IgM/κ (21.7%), IgM/λ (13.1%), IgG/κ (13.1%), λ (13.1%), IgA/κ (4.3%), IgG/λ (4.3%). Morphological spectrum of non-amyloid MGRS is shown in the figure 2. Combination of light chain deposition disease and thrombotic microangiopathy was documented in two cases. The majority of patients (82.7%) was treated with clone-specific agents. In non-IgM-associated MGRS cases bortezomib+dexamethasone (D) (n=11), melphalan+D (n=2), cyclophosphamide (CPh) +bortezomib+D (n=1), lenalidomide+D (n=1) were used. Autologous stem cell transplantation was performed in 1 case. Prednisolone+CPh based schemes were applied in 5 patients. In IgM-associated MGRS 7 patients were treated with rituximab and 1 patient with bortezomib+D due to contraindication to anti-CD20 agent. 8 patients were missed from the follow-up. HR and RR were achieved in 76.2% and 62% of the treated patients, respectively (Figure 3). The five-year cumulative renal survival was 44% in the non-amyloid MGRS group and did not significantly differ from renal AL-amyloidosis group when compared (Figure 4). Conclusion Non-amyloid type of MGRS is a clinically and morphologically diverse entity characterized by a poor renal prognosis, especially in the absence of clone-specific therapy. Treatment of MGRS should be carried out in a timely manner with the participation of a hematologist and nephrologist in order to prevent loss of kidney function and increase life expectancy.

Perioperative use of serum creatinine and postoperative acute kidney injury: a single-centre, observational retrospective study to explore physicians\u2019 perception and practice

BackgroundPostoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians’ attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease.MethodsAdult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m2 at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI.ResultsA total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys.ConclusionPO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients.Trial registrationClinicalTrials.gov, NCT04341974.

Urinary abnormality in mixed connective tissue disease predicts development of other connective tissue diseases and decrease in renal function.

To clarify the clinical significance of development of urinary abnormality in mixed connective tissue disease (MCTD). Forty-one patients with an initial diagnosis of MCTD, followed at five hospitals between April 1, 2000 and December 31, 2013, were included. The relationship between urinary abnormality and various clinical parameters were retrospectively analyzed. Urinary abnormality was defined as proteinuria and/or hematuria detected by urinalysis. Development of other connective tissue diseases (CTDs) was defined as satisfaction of the criteria of each respective disease. Of 41 patients (34 females, 7 males, mean age at diagnosis 42.2 ± 15.2 years), 16 developed urinary abnormality (UrA(+) patients). The total incidences of development of other CTDs were higher in the UrA(+) patients than UrA(-) (62.5% versus 16.0%, p = .01). In the comparison between UrA(+) and UrA(-) patients, there were no significant differences in follow-up duration or last determined estimated glomerular filtration rate (eGFR), although eGFR decreased more significantly in the UrA(+) patients than UrA(-). (-20.2 ± 17.2 vs -6.1 ± 13.8 ml/min/1.73m2, p = .01; -21.0 ± 18.9 vs -6.7 ± 14.1%, p = .03). Urinary abnormality during the clinical course in MCTD is predictive of a higher incidence of developing other CTDs. Furthermore, it might also predict long-term renal prognosis in patients with an initial diagnosis of MCTD.

Long-term clinical characteristics and renal prognosis of children with tubulointerstitial nephritis and uveitis syndrome.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, especially in children. Owing to the short-term observational period and the small number of patients analyzed in previous reports, the long-term clinical and laboratory characteristics and renal prognosis of children with TINU syndrome remain unclear. In this retrospective observational study, we enrolled 29 children with TINU syndrome from February 1990 to February 2019. During the median follow-up duration of 38 months, the kidney function, urinary β2 microglobulin-creatinine ratio (U-β2MG/Cr), and uveitis in the patients had significantly improved at 24, 6, and 36 months after diagnosis. Higher U-β2MG/Cr was associated with longer duration of kidney function normalization. Half of the patients required uveitis treatment for 5 years after the diagnosis. Patients with severe low-molecular weight proteinuria at diagnosis needed a longer duration to achieve improvements in kidney function. Uveitis has a much longer treatment period than tubulointerstitial nephritis. This study demonstrates the good prognosis of children with TINU syndrome in terms of their long-term clinical and laboratory characteristics.

Effects of transient acute kidney injury, persistent acute kidney injury and acute kidney disease on the long-term renal prognosis after an initial acute kidney injury event.

To clarify the effects of the duration of acute damage and/or loss of renal function following an acute kidney injury event on the renal prognosis after recovery. We retrospectively reviewed data collected between 1995 and 2016 from the Kochi Medical School Hospital. Patients were stratified according to the time required for recovery with fluid therapy (expected to reflect the presence of renal dysfunction): ≤2 days after onset, transient injury group (n = 491); 3 to 7 days after onset, persistent injury group (n = 1076); and ≥ 8 days after onset, acute kidney disease group (n = 1046). The healthy group comprised 1000 randomly selected adult patients without acute kidney injury with at least two creatinine measurement results during the study. Survival time was defined as the time from recovery to a 30% decrease in the estimated glomerular filtration rate (primary endpoint). Kaplan-Meier and Cox proportional hazards analyses were conducted. Event incidence rates were higher for the transient injury, persistent injury and acute kidney disease groups than for the healthy group. Persistent injury and acute kidney disease presented a higher risk of renal function decline than transient injury following recovery. Transient acute kidney injury, persistent acute kidney injury and acute kidney disease resulted in functional decline and rapid chronic kidney disease progression risks despite recovery. Transient acute kidney injury recovery within 2 days could be associated with better long-term prognoses than persistent acute kidney injury and acute kidney disease persisting beyond 2 days.

Critically ill, tubular injury, delayed early recovery: characteristics of acute kidney disease with renal oxalosis

Objects This study aimed to analyze the clinicopathological features of acute kidney disease (AKD) with renal oxalosis. Methods Data for biopsy-proven AKD with oxalosis diagnosed from Jan 2011 to Oct 2018 was collected. The underlying diseases, dietary habits, clinical and pathological characteristics of newly emerging kidney disease were analyzed. The long-term renal prognosis was observed. Results A total of 23 patients were included, comprised of 18 men and 5 women with a mean age of 51.6 ± 15.9 years. The peak Scr was 669.9 ± 299.8 μmol/L, and 95.7% of patients had stage 3 acute kidney injury (AKI). Drug-induced tubulointerstitial nephritis (TIN) was the most common cause (65.2%) of AKD, followed by severe nephrotic syndrome (17.4%). All patients had pathological changes indicating TIN, and 11 patients were complicated with the newly emerging glomerular disease (GD). The risk of oxalosis caused by increased enterogenous oxalate absorption accounted for only 26.1%, and others came from new kidney diseases. The majority (75%) of abundant (medium to severe) oxalosis occurred in patients without GD. There were no significant differences in the score for tubular injury (T-IS) and interstitial inflammation with different severities of oxalosis. Rate of Scr decrease (ΔScr%) at 2 weeks was negatively correlated with the severity of oxalosis (R = −0.542, p = 0.037), score for T-IS (R = −0.553, p = 0.033), and age (R = −0.736, p = 0.002). The decrease in Scr at 4 weeks was correlated with T-IS (R = −0.433), but had no correlation with oxalosis. Conclusions The present findings revealed that 95.7% of AKD with secondary renal oxalosis occurred in critically ill patients. AKD from tubular injury was the prominent cause. Severe oxalosis contributed to delayed early recovery of AKD.

Clinical and morphological spectrum and long-term outcome in monoclonal gammopathy of renal significance: one center study

INTRODUCTION AND AIM . Monoclonal gammopathy of renal significance (MGRS), heterogeneous nosological entity, is caused by monoclonal immunoglobulin (IG) produced by a "small" B-cell lineage clone. The analysis of long-term renal prognosis in various clinical and morphological types of disease and in different degrees of hematological response (HR) in the Russian patient cohort became the goal of this study. PATIENTS AND METHODS . Patients met the criteria of MGRS (morphologically verified monoclonal IG related kidney damage, an aberrant clone in the bone marrow and/or the level of serum/urine paraprotein not met the oncohematological criteria for treatment initiation) were enrolled in this one-center prospective study from 01.01.2011 till 01.03.2020. The morphological spectrum of MGRS, types of therapy, hematological and renal responses (RR) were analyzed. HR was assessed depending on the type of monoclonal IG according to the accepted criteria. The presence of RR was considered as a decrease in daily proteinuria&gt; 30 % from the initial level or less than 0.5 g in the absence of a decrease in eGFR&gt; 25 % at the time of the end of follow-up. The progression of renal dysfunction was documented with a decrease in eGFR&gt; 25 % from baseline. Renal outcome (initiation of renal replacement therapy or eGFR &lt;15 ml/min/1.73m2 at the end of follow-up) and death were determined. Long-term renal survival was assessed by the Kaplan-Meier method. The median follow-up period was 18 (4; 38) months. RESULTS . The incidence of MGRS was 4.9 % (n = 102) of all performed kidney biopsies (n = 2042), the majority of cases represented with AL amyloidosis (AL, n = 73; 71.6 %). In cases of non-amyloid variant of MGRS (non-AL MGRS, n=29, 28.4 %) the most common types of renal injury were light chain deposition disease (27,6 %) and proliferative glomerulonephritis with deposition of monoclonal IG (27.6 %). The majority of patients (80.4 %) was treated with clone-specific agents, autologous bone marrow transplantation was performed in 13 cases. HR was achieved in 74 % and 80 % of the treated patients with AL and non-AL MGRS, respectively. RR was obtained in 42 % of patients with AL and in 62 % of patients with non-AL MGRS. The five-year cumulative renal survival did not differ significantly between the groups: 66 % in AL and 44 % in non-AL MGRS ( р =0,78). Cumulative renal survival in patients who did not achieve HR was significantly lower (42 %) than in cases with complete HR (86 %), p =0.0014. CONCLUSION . MGRS is a clinically and morphologically heterogeneous nosological entity characterized by a poor renal prognosis, especially in the absence of clone-specific therapy. Treatment in MGRS should be carried out in a timely manner with the participation of a hematologist and nephrologist in order to prevent loss of kidney function and increase life expectancy.

Mixed cryoglobulinemic glomerulonephritis and vasculitis in primary Sjögren’s syndrome

Introduction: Cryoglobulinemia is a condition where complexes of one or more different classes of immunoglobulins precipitate at low temperatures and become soluble again at higher temperatures. Cryoglobulins are typically categorized as types I to III, based on their immunoglobulin composition. Mixed cryoglobulinemia (type II and III) is most often associated with constitutional symptoms, such as fatigue, myalgia, arthralgia, sensory or motor changes (peripheral neuropathy) and palpable purpura (cutaneous vasculitis). Twenty to thirty percent of the affected patients suffer from membranoproliferative glomerulonephritis. Case Presentaion: We discuss a case of a 45-year-old woman with a history of Sjogren’s syndrome and mixed cryoglobulinemia who presented with acute renal failure, nephritic syndrome, vasculitislike rash on the legs and non-healing skin ulcer. Further investigations confirmed type II mixed cryoglobulinemia associated with cutaneous leukocytoclastic vasculitis and membranoproliferative glomerulonephritis leading to end-stage renal disease (ESRD). Conclusion: Mixed cryoglobulinemia secondary to primary Sjogren’s syndrome (pSS) is rare and reported in 22.5% of cases of non-infectious cryoglobulinemic glomerulonephritis. Long-term renal prognosis is good with only 9% of these patients evolving to ESRD. Nevertheless, the long-term overall survival is poor with severe infections as the leading cause of death.

303-OR: Effect of Dapagliflozin on Risk for Fast Decline in EGFR: Analyses from the DECLARE-TIMI 58 Trial

SGLT2 inhibitors may lead to short term decrease in eGFR, with later stabilization and long-term reduction in the risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as a reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post-hoc analysis we studied the effect of dapagliflozin (dapa) on the risk for FD in the DECLARE-TIMI 58 trial. In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for a median of 4.2 years. The risk for FD was compared between treatment arms. In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1% respectively, p<0.0001). This observation was persistent in all subgroups assessed (Table). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in the FD (N=4,788) vs. non-FD (N=10,224) patients. The proportion of patients with FD during the entire study period (i.e., 0-4 years) was reduced with dapa vs. placebo as well (33.6% vs. 37.0% respectively, p<0.0001). Dapagliflozin reduced the risk for FD in eGFR in a broad population of patients with T2D and either established or increased risk for CVD, but relatively preserved renal function, irrespective of patients’ baseline characteristics.

Long-term renal prognosis among patients with primary Sjögren's syndrome and renal involvement: A nationwide matched cohort study

BackgroundThe long-term renal outcome in patients with primary Sjögren's syndrome (pSS) remains uncertain. We aimed to determine the absolute incidence and relative risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in patients with pSS at the general population level. MethodsWe performed a retrospective cohort study using a national health insurance database in Taiwan from 2000 to 2013. We calculated the cumulative incidence of CKD and ESRD in our pSS and age-, sex- and entry time-matched control cohorts. Cox regression analyses were used to estimate adjusted hazard ratios (aHRs) after adjusting for comorbidities and medications. ResultsAmong 17 505 patients with incident pSS, 1008 (5.8%) developed CKD and 38 (0.22%) developed ESRD. Of the 87 525 non-pSS controls, 3173 (3.6%) developed CKD and 256 (0.29%) developed ESRD. The risk of CKD was higher in patients with pSS than in the non-pSS controls (adjusted hazard ratio [HR] 1.49, 95% confidence interval [95% CI] 1.38–1.59). Notably, the risk of ESRD was similar in both pSS and non-pSS cohorts (aHR 0.82, 95% CI 0.58–1.16). ConclusionsRenal prognosis among patients with pSS and renal involvement is good. Although the risk of ESRD did not increase in patients with pSS, a significantly increased risk of CKD was observed in these patients, indicating the need for increased vigilance in regular monitoring for renal complications in patients with pSS.

Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: A long-term follow-up study.

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 μm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 μm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 μm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 μm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor.

Time-averaged proteinuria during follow-up and renal prognosis in patients with biopsy-proven benign nephrosclerosis.

Heavy proteinuria at diagnostic renal biopsy has been reported as an independent risk factor for deteriorating renal function in benign nephrosclerosis (BNS). However, studies investigating the relationship between the amount of proteinuria during follow-up and long-term renal prognosis in BNS are limited. This study aimed to assess the relationship between time-averaged proteinuria (TAP) and renal prognosis in BNS. The study participants included 98 patients with biopsy-proven BNS (average age 52 ± 13years, estimated glomerular filtration rate (eGFR) 53 ± 25ml/min/1.73 m2, urine protein excretion at baseline 1.34 ± 1.30g/gCr) from the Jikei University Hospital. Multivariate analysis was used to investigate the effects of TAP and other clinicopathological findings on the risk for renal outcome in biopsy-proven BNS (a 30% decline in eGFR from baseline or end-stage renal disease). Proteinuria was measured every 6months and the mean value was used as an indicator of TAP. The average observation period was 56 ± 43months. In the unadjusted model, higher levels of TAP and urinary protein at baseline, glomerulosclerosis, and tubulointerstitial damage were associated with renal prognosis. The adjusted model demonstrated a significant association between TAP and renal outcomes (hazard ratio 5.45, 95% confidence interval 3.02-10.7), which was independent of higher baseline proteinuria, glomerulosclerosis, and tubulointerstitial damage. TAP is an independent risk factor for renal prognosis in patients with BNS, indicating the significance of urinary protein excretion during follow-up for the progression of BNS. Clinicians should understand the importance of follow-up evaluation for proteinuria in patients with BNS.

Review on long‐term non‐renal complications of childhood nephrotic syndrome

Nephrotic syndrome (NS) is the most common glomerular childhood disease. A body of literature has described the long-term renal prognosis of childhood-onset idiopathic NS. However, the nonrenal outcomes have not been studied as much. We aimed to discuss the long-term non-renal outcomes of childhood NS, highlighting studies with a follow-up period of more than 10 years. We reviewed the literature and found that a number of immunosuppressive agents have stopped inflammation, stabilised the podocyte cytoskeleton and reduce proteinuria. However, prolonged treatment has frequently been associated with a high risk of renal and non-renal complications in patients with a complicated disease course, defined as frequent relapses or steroid dependency. Non-renal complications may include impaired longitudinal growth and pubertal development, undesirable fertility outcomes, ocular complications, bone mineral diseases and potential malignancies. This review discusses and summarises the non-renal outcomes of idiopathic childhood NS.

Impact of hypertensive emergency and rare complement variants on the presentation and outcome of atypical hemolytic uremic syndrome.

A typical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. Hypertensive emergency, characterized by elevation of systolic (>180 mmHg) or diastolic (>120 mmHg) blood pressure together with end-organ damage, can cause thrombotic microangiopathy which may mimic aHUS. We retrospectively evaluated the clinical, biological and complement genetic characteristics of 76 and 61 aHUS patients with and without hypertensive emergency, respectively. Patients with hypertensive emergency-aHUS were more frequently males, with neurological involvement, and a slightly higher hemoglobin level. At least one rare complement variant was identified in 51.3% (39/76) and 67% (41/61) patients with or without hypertensive emergency, respectively (P=0.06). In both groups, renal prognosis was severe with 23% and 40% of patients reaching end-stage renal disease after a 5-year follow-up (P=0.1). The 5-year renal survival was 77% in patients without hypertensive emergency or a complement variant, and below 25% in the three groups of patients with hypertensive emergency and/or a complement variant (P=0.02). Among patients without hypertensive emergency, the 5-year renal survival was 100% vs. 40% in those treated or not with eculizumab, respectively (P<0.001). Conversely, the 5-year renal survival of patients with hypertensive emergency was 46% vs. 23% in those treated or not with eculizumab, respectively (P=0.18). In conclusion, information on the presence or absence of hypertensive emergency and rare complement variants is essential to stratify the long-term renal prognosis of patients with aHUS.

Once-Daily Low-Dose Cyclosporine A Treatment with Angiotensin Blockade for Long-Term Remission of Nephropathy in Frasier Syndrome

Cyclosporine A is known to be effective in some genetic podocyte injury. However, the efficacy of cyclosporine A depends on the degree of histopathological findings, and the relationship between long-term use and renal prognosis remains unknown. Frasier syndrome is a rare genetic disorder caused by intronic mutations in WT1, and is characterized by progressive glomerulopathy, a 46,XY disorder of sex development, and an increased risk of gonadoblastoma. We report here a 16-year-old phenotypically female patient with Frasier syndrome. A renal biopsy at the age of seven years showed segmentally effaced podocyte foot processes with no evidence of glomerulosclerosis. Steroid-resistant proteinuria progressed to the nephrotic range at the age of 10 years, which responded to once-daily administration of cyclosporine A with low two-hour post-dose cyclosporine A (C2) levels; she then achieved stable partial remission in combination with renin-angiotensin system (RAS) blockade. At the age of 12 years, examinations for delayed puberty confirmed the diagnosis of Frasier syndrome. The second renal biopsy showed widespread foot process effacement and a minor lesion of segmental glomerulosclerosis without findings suggestive of cyclosporine A nephropathy. She maintained partial remission and normal renal function with the continuation of once-daily low-dose cyclosporine A. The C2 levels required for the remission were between 212 and 520 ng/ml. Cyclosporine A dosages sufficient for maintaining the C2 levels were 1.1-1.2 mg/kg per day. In conclusion, the long-lasting treatment of once-daily low-dose cyclosporine A with RAS inhibition was effective for induction and maintenance of partial remission in Frasier syndrome.