Presence Of Nephrotic Range Proteinuria Research Articles

Dyslipidemia in children with chronic kidney disease—findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study

BackgroundDyslipidemia is an important and modifiable risk factor for CVD in children with CKD.MethodsIn a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3–5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis.ResultsA total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure.ConclusionsDyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

#6323 RENAL CONTRAST-ENHANCED ULTRASOUND AND GLOMERULONEPHRITIS: A GOOD MARKER OF DISEASE ACTIVITY

Abstract Background Contrast-enhanced ultrasound (CEUS) could provide a lot of information of renal blood flow. Renal blood flow is an excellent marker of inflammatory and fibrotic processes in the kidney such as glomerulonephritis. Therefore, in patients with these diseases, renal CEUS can be both a prognostic marker and an index of response to therapy. Currently in the literature there are preliminary studies showing the role of CEUS in terms of histology and outcome in the evaluation of patients with glomerulonephritis. In this pilot study we used perfusion CEUS parameters (WiR and WoR; WiAUC and WoAUC) as possible markers of renal microvascular damage. We compared the perfusion parameters with the clinical and histological findings of our patients. Method Eighteen patients with clinical and laboratory signs of glomerulonephritis were enrolled. All patients underwent ultrasound-assisted renal biopsy and B-mode ultrasound examination, color Doppler ultrasound and contrast-enhanced ultrasound. Time Intensity (TI) curves were obtained from renal CEUS. TI curves and several quantitative perfusion parameters were defined using VueBox® Quantitation Software. Results From April to October 2022, 18 patients (12 men and 6 women) with clinical and laboratory suspicion of glomerular disease were enrolled. Median age was 48.05 years, all patients underwent renal biopsy and contrast-enhanced ultrasound at basal condition. Table 1 shows patients characteristics. CKD patients were stratified into two groups according to their eGFR: group I (eGFR < 60 ml/min/1.73 m2, n. = 4) and group II (eGFR ≥ 60 ml/min/1.73 m2, n. = 3). Moreover, we divided patients into two groups based on the presence of nephrotic-range proteinuria (≥ 3.5 g/24h). At this time, seven patient data are suitable for analysis. The small sample size at present does not allow for statistical significance. However, in our study, the persistence of contrast agent signal during the wash-out phase was differed markedly in correlation with the degree of CKD. In particular, we observed a slower wash-in phase in the presence of vascular hyalinosis (Fig. 1). Conclusion Our experience seems to confirm that CEUS parameters can be excellent indicators both in terms of patient disease outcomes and histological data. CEUS can effectively and quantitatively demonstrate renal microvascular perfusion in patients with glomerulonephritis. Future goal is that CEUS could also be a prognostic and follow-up marker after renal biopsy in patients with glomerulonephritis.

Changing Tides of Acute Interstitial Nephritis: A Retrospective Observational Study from South India.

The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease. AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease.

MO216: The Importance of Nephrotic Range Proteinuria in Renal Survival of Patients With IGA Nephropathy

Abstract BACKGROUND AND AIMS Persistent proteinuria (urinary protein level [UPr]>1 g/24 h) and especially nephrotic range proteinuria, is a poor prognostic factor in IgA nephropathy. Patients with proteinuria > 3.5 g/24 h have a 24-fold faster decline of renal function as compared with those with < 1g/24 h. The aim of this study was to explore the relationship between nephrotic range proteinuria and renal survival in patients with IgA nephropathy. METHOD All records from patients who were followed in a renal outpatient clinic and had a biopsy-proven IgA nephropathy were retrospectively screened. Patients with nephrotic range proteinuria (UPr > 3.5 g/24 h) at the time of diagnosis were compared, regarding their clinical and epidemiological characteristics, with patients with lower levels of proteinuria. Renal survival was defined as the absence of end-stage kidney disease [estimated Glomerular Filtration Rate (eGFR)≤15 mL/min/1.73 m2] or/and a ≥ 50% reduction of eGFR from baseline values. RESULTS We included 53 patients with IgA nephropathy. Their mean age was 46.24 (±16.92) and the median follow-up time was 49 (17–111) months. The median UPr value at the time of diagnosis was 1.89 (0.83–3.50) g/24 h and 17 patients had UPr > 3.5 g/24 h. Patients with nephrotic range proteinuria had worse renal function (eGFR 29 versus 73 mL/min/1.73 m2 P < .001), developed more frequently hypertension (82.35% versus 50%, P = .02) and rapidly progressive glomerulonephritis (23.53% versus 5.56%, P = .05) compared with those with lower levels of proteinuria. The episodes of macroscopic hematuria were less frequent in the group of patients with nephrotic range proteinuria (11.76% versus 38.89%, P = .05). Regarding patients treated with prednisone, the mean daily dose of prednisone was 23.42 mg for the nephrotic patients versus 16.61 mg for the patients with UPr < 3.5 g/24 h (P = .03). Proteinuria > 3.5 g/24 h was an independent risk factor for poor renal survival (HR 15.48, P = .01). The 5-year renal survival of patients with nephrotic range proteinuria was reduced compared with those with lower levels of proteinuria (66.64% versus 100%). CONCLUSION This study showed that the presence of nephrotic range proteinuria at the time of diagnosis was an independent risk factor for reduced renal survival. This relationship persisted after sex, age and renal function adjustment at the time of diagnosis.

Primary Focal Segmental Glomerulosclerosis Recurrence After Pediatric Renal Transplantation.

Focal segmental glomerulosclerosis recurrence after renal transplant occurs frequently in pediatric patients and is associated with poor graft survival when patients reach adulthood. We investigated recurrence rates, recurrence risk factors, management strategies, and long-term graft function among pediatric renal transplant recipients with focal segmental glomerulosclerosis as primary disease. We retrospectively evaluated medical records of 34 pediatric patients with primary focal segmental glomerulosclerosis who had undergone renal transplant between 2004 and 2019 at our center. Focal segmental glomerulosclerosis recurrence was diagnosed by the presence of nephrotic range proteinuria after transplant and confirmed by graft biopsy. Preoperative prophylactic plasma exchange was administered to pediatric renal transplant recipients with primary focal segmental glomerulosclerosis. Plasma exchange was also used to treat focal segmental glomerulosclerosis recurrence, with rituximab added if the patient did not respond to plasma exchange. All patients (male-to-female ratio of 19:15) in our group underwent renal transplant. Mean patient age at the time of transplant was 12.72 ± 5.46 years. Twenty-nine patients received living- related donor allografts (85.3%) and 5 received organs from deceased donors (14.7%). We identified focal segmental glomerulosclerosis recurrence in 5 recipients (14.7%). Time from focal segmental glomerulosclerosis diagnosis to end-stage renal disease and duration of dialysis were shorter in the recurrence group than in the nonrecurrence group (48.4 months [range, 2-90 mo] vs 65.1 months [range, 8-123 mo] and 1.41 ± 0.82 vs 3.18 ± 1.88 years, respectively; P < .05). Donor type and transplant age were similar in both groups. Of those with recurrence who had received plasma exchange and rituximab, 3 patients (75%) had complete remission and 1 patient (25%) had partial remission. Prophylactic plasma exchange and the combined plasma exchange-rituximab regimen for treatment of focal segmental glomerulosclerosis recurrence resulted in low recurrence and good remission rates in our pediatric cohort.

Occult Kidney Dysfunction in Children With Transfusion-Dependent Thalassemia.

Background: Thalassemia is the commonest hemoglobinopathy in Southeast Asia. Kidney dysfunction is an underreported sequelae in children with thalassemia. We conducted a retrospective study to identify the prevalence of and predisposing factors for kidney dysfunction in children with transfusion-dependent thalassemia (TDT).Method: Abnormal kidney function was defined as children with a glomerular filtration rate (GFR) of <90 ml/min/1.73 m2 or a decline in GFR of >20 ml/min/1.73 m2 or presence of nephrotic range proteinuria within 3 years of commencing regular (every ≤6 weeks) red cell transfusion. Data analyzed were age at diagnosis of thalassemia, number of transfusion-years, iron chelation therapy, serum ferritin, and pre-transfusion hemoglobin levels.Results: Eighty-one children were studied. Mean age was 11.72 ± 5.275 years. Thirty out of 81 (37%) demonstrated abnormal kidney function. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit. This fraction was doubled [48/81 (59.3%)] when the cohort was tracked back by 3 years from the last clinic encounter. Age at diagnosis (RR, 1.157; 95% CI, 1.014–1.319; p = 0.03) and duration of receiving transfusions (RR, 0.984; 95% CI, 0.974–0.994; p = 0.001) were associated with increased risk of developing abnormal kidney function.Conclusion: Abnormal kidney function in children with TDT may be overlooked by medical personnel without active screening measures. Children receiving regular red cell transfusions require systematic surveillance to enable early detection of kidney dysfunction and timely implementation of appropriate therapeutic interventions.

A Retrospective Study of Clinical and Economic Burden of Focal Segmental Glomerulosclerosis (FSGS) in the United States

IntroductionInformation on the economic burden of focal segmental glomerulosclerosis (FSGS) is sparse. This study characterized health care resource utilization (HCRU) and costs in patients with FSGS, and evaluated the impact of nephrotic range proteinuria on these outcomes.MethodsThis retrospective, observational cohort study used administrative claims data from the Optum Clinformatics Data Mart Database from October 2015 to December 2019. Patients with FSGS (n = 844; first claim = index event) between April 2016 and December 2018 were matched on index date, age, sex, and race to non-FSGS controls (n = 1688). FSGS nephrotic range (urine protein/creatinine ratio >3000 mg/g or albumin/creatinine ratio >2000 mg/g) and non-nephrotic subpopulations were identified. Baseline comorbidities, 12-month post-index all-cause HCRU and costs (per patient per year [PPPY]), and immunosuppressant prescriptions were compared between matched cohorts and between FSGS subpopulations.ResultsComorbidity burden was higher in FSGS. Of 308 patients with available urine protein/creatinine ratio/albumin/creatinine ratio results, 36.4% were in nephrotic range. All-cause HCRU was higher in FSGS across resource categories (all P < 0.0001); 50.6% of FSGS and 23.3% of controls were prescribed glucocorticoids (P < 0.0001). Mean total medical costs were higher in FSGS ($59,753 vs. $8431 PPPY; P < 0.0001), driven by outpatient costs. Nephrotic range proteinuria was associated with higher all-cause inpatient, outpatient, and prescription costs versus nonnephrotic patients (all P < 0.0001), resulting in higher total costs ($70,481 vs. $36,099 PPPY; P < 0.0001).ConclusionsFSGS is associated with significant clinical and economic burdens; the presence of nephrotic range proteinuria increased the economic burden. New treatment modalities are needed to reduce proteinuria, help improve patient outcomes, and reduce HCRU and associated costs.

MO513CLINICAL AND ECONOMIC BURDEN OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) IN THE UNITED STATES: A RETROSPECTIVE, OBSERVATIONAL COHORT STUDY

Abstract Background and Aims The burden of disease associated with FSGS has not been well characterized, especially with regard to health care resource utilization (HCRU) and related costs. The aim of this study was to evaluate all-cause HCRU and estimate associated costs in patients with FSGS compared with a matched non-FSGS cohort; a secondary aim was to evaluate the impact of nephrotic range proteinuria on these outcomes. Method Data were from the Optum Clinformatics® Data Mart Database. Patients with ≥ 1 claim (1st claim = index event) for FSGS between April 2016 and December 2018 were identified based on ICD-10-CM codes and matched 1:2 (FSGS:controls) on index date, age, sex, and race to non-FSGS controls; continuous enrollment 6 months pre- and 12 months post-index was required. FSGS nephrotic range (either UPCR &amp;gt;3000 mg/g or ACR &amp;gt;2000 mg/g) and non-nephrotic subpopulations were also identified. Quan-Charlson Comorbidity Index (CCI) and individual comorbidities at baseline, and 12-month post-index all-cause HCRU and associated costs (per patient per year [PPPY]) as well as medication prescriptions related to FSGS treatment were compared between the matched cohorts and between the FSGS subpopulations; t-tests were used for continuous variables and chi-square tests for categorical variables. Results 844 patients with FSGS were matched with 1688 non-FSGS controls; 57.4% male, 56.9% white, mean (SD) age 54.7 (18.4) years. Mean (SD) CCI was higher in the FSGS cohort relative to matched controls (2.72 [2.12] vs 0.55 [1.29]; P &amp;lt; .0001), with prevalence of most individual comorbidities higher in the FSGS cohort. Only 308 FSGS patients (36.5%) had UPCR or ACR tests with available results during the review period; 112 (36.4%) were in the nephrotic range and 196 were non- nephrotic (63.6%). The FSGS cohort was characterized by higher rates of all-cause HCRU across resource categories (all P &amp;lt; .0001) (Table 1); outpatient visits was the most frequently used category (99.1% vs 69.0%), followed by prescription medications. Among patients who used these resources, units of use were significantly higher in FSGS vs matched controls except for length of stay (Table 1). Readmission rates following 1st post-index hospitalization were higher in the FSGS cohort vs matched controls at 30 days (16.1% vs 6.0%; P &amp;lt; .05) and 365 days (39.1% vs 22.9%; P &amp;lt; .05). Glucocorticoids were the most frequently prescribed FSGS-related medication in both cohorts, with a higher rate in FSGS vs matched controls (50.6% vs 23.3%; P &amp;lt; .0001); other FSGS-related medications were infrequently prescribed (&amp;lt; 14%). Inpatient, outpatient, and prescription costs were higher in the FSGS cohort vs matched controls (all P &amp;lt; .0001) resulting in mean total annual medical costs of $59,753 vs $8,431 PPPY (P &amp;lt; .0001) that were driven by outpatient costs (Fig. 1A). Nephrotic range proteinuria was associated with higher all-cause inpatient, outpatient, and prescription costs vs non-nephrotic patients (all P &amp;lt; .0001; Fig. 1B), resulting in higher total costs ($70,481 vs $36,099 PPPY; P &amp;lt; .0001). A higher proportion of nephrotic range patients were prescribed FSGS-modifying medications (73.2% vs 54.1%; P = 0.001), with glucocorticoids the most frequent medication. However, 26.8% of nephrotic range patients were not prescribed any FSGS-related medications. Conclusion FSGS is associated with significant clinical and economic burdens with total annual medical costs &amp;gt; 7-fold higher than matched controls that were driven by outpatient costs. The presence of nephrotic range proteinuria substantially and significantly increased the economic burden. New treatment modalities leading to lower rates of proteinuria may help improve patient outcomes while reducing HCRU and their associated costs.

Preeclampsia for the Nephrologist: Current Understanding in Diagnosis, Management, and Long-term Outcomes.

Preeclampsia is a multisystem progressive disorder of pregnancy that can be potentially catastrophic for the mother and the fetus. It involves complex perturbations of the kidney and systemic physiology, along with long-term effects on vascular and kidney health. Thus, the nephrologist plays a key role in the peripartum and long-term management of preeclampsia. Recent translational research has improved our understanding of its pathophysiology, and there is hope for novel therapies. In this review, we discuss the evolution of diagnostic criteria and dilemmas in the diagnosis of hypertensive disorders in pregnancy. We summarize the advances in the pathogenesis and prediction of preeclampsia. We describe the management and prevention of preeclampsia focusing specially on the forthcoming strategies from the nephrologist's perspective. We address the evidence regarding long-term outcomes for the mother and the child. We end with exploring areas warranting future research.

Value of monitoring urine ammonia at time of biopsy in patients with lupus nephritis

ObjectiveAlthough lupus nephritis (LN) is mostly characterized by glomerular involvement, tubular injury is indispensable in its pathogenesis and progression. The purpose of this study is to examine associations between urinary acidification function and clinical and pathological features in LN.MethodsA total of 103 patients with renal biopsy-proven LN were included, and clinical parameters and laboratory data were obtained from the medical records. Plasma samples, 24-h urine samples and the urinary acidification function, including urine pH, titratable acid, and ammonia, were collected within 3 days before the day of renal biopsy. The correlations between defects of acid excretion and clinical and pathological features were then assessed. Logistic regression analysis was used to assess factors associated with the presence of nephrotic range proteinuria.ResultsThe urine ammonia level was inversely correlated with SLEDAI-2 K scores, rSLEDAI scores, serum creatinine levels and proteinuria, while it was positively correlated with eGFR. And urine titratable acid was only inversely correlated with rSLEDAI scores and proteinuria. Moreover, urine ammonia had significant negative correlations with AI scores, interstitial inflammatory cell infiltration, CI scores, glomerular sclerosis, fibrous crescents, tubular atrophy and interstitial fibrosis. And urine titratable acid was mainly inversely correlated with CI scores. Furthermore, univariate logistic analyses identified that both urine titratable acid and ammonia were correlated with the presence of nephrotic range proteinuria. After the adjustment for chronicity index and eGFR in a multivariate logistic analysis, only urine titratable acid was still identified as an independent risk factor for the occurrence of nephrotic range proteinuria.ConclusionsUrine ammonia was associated with clinical and pathological features of chronicity and tubulointerstitial disease activity among patients with lupus nephritis. Furthermore, the strong association between urinary protein and titratable acid excretion at the time of kidney biopsy is significant even after adjusting for the chronicity index and eGFR at biopsy.

The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. This was a prospective study in which 127 children (age range 8-17years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit. The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p = 0.02) and PedsQL social functioning (p < 0.01). The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument.

Erratum to: Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome

The original version of this article unfortunately contained errors. In the ‘‘Methods’’ section of the main text, under the heading ‘‘Participants’’, the sentences that begin with ‘‘Remission’’ and ‘‘No response’’ should read: Remission was defined as complete (Up/Uc \0.2 mg/ mg) or partial (Up/Uc between 0.2 and 2 mg/mg, serum albumin [2.5 g/dL, and no edema). No response was the presence of nephrotic range proteinuria (Up/Uc [2 mg/ mg), serum albumin \2.5 g/dL, or edema. In Table 2, in the first column, for the line ‘‘Spot Up/ Uc’’, the unit should be ‘‘mg/mg’’. In Table 3, in the first column, for the line ‘‘Total duration of illness (years)’’, the value of SRNS without subclinical hypothyroidism, and the unit for the line ‘‘Cumulative dose of prednisolone’’ were shown incorrectly. The corrected tables are as follows:

Linkage and Association Study of Neurotrophins and Their Receptors as Novel Susceptibility Genes for Childhood IgA Nephropathy

Neurotrophins (NTs) and their receptors (NTRs) are known to be important for pathogenesis of various inflammatory diseases that occur in not only neuronal but also nonneuronal tissues, including kidney. Here, we investigated association between childhood IgA nephropathy (IgAN) and single nucleotide polymorphisms (SNPs) of genes encoding NTs [nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)] and NTRs [nerve growth factor receptor (NGFR) and neurotrophic tyrosine kinase receptor 1-3 (NTRK1-3)]. The genotyping data of 197 patients and 289 control subjects revealed significant association between NGF SNP rs11102930 and presence of IgAN. Patient subgroup analysis revealed that that the presence of nephrotic range proteinuria (>40 mg/m/h) was associated with rs6334 of NTRK1 and rs11030104, rs7103411, rs7103873, and rs6484320 of BDNF. Significant genotype differences were observed in podocyte foot process effacement for rs1187321 and rs1187323 of NTRK2. Furthermore, some SNPs showed significantly different genotype distribution between patients with or without pathologically advanced disease markers, specifically in rs6334 of NTRK1. Our results suggest that SNPs of NTs and NTRs are associated with susceptibility, pathological advancement, podocyte foot process effacement, and development of proteinuria in childhood IgAN.

Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation

FSGS has a high recurrence rate after renal transplantation. To examine the effects of the use of preemptive and post-transplant PP on recurrence and graft outcome, we conducted a retrospective study on 34 pediatric patients (mean age 13±5 yr) with biopsy-proven pretransplant FSGS and who underwent a renal transplantation between 1996 and 2007. Recurrence was defined as a serum albumin level of <3.0g/L in the presence of nephrotic-range proteinuria (>40mg/m(2) /h). Total response to PP therapy was defined as the resolution of the nephrotic-range proteinuria and partial response as persistent proteinuria despite PP but not in the nephrotic range. Fifteen patients received a LD renal transplantation and 19 patients received a DD renal transplantation. Nineteen patients received CsA and 14 patients received tacrolimus. Nineteen patients (56%) had FSGS recurrence. There was no difference in the recurrence rate between patients receiving CsA vs. tacrolimus. Among the 15 LD patients, 13 received preemptive PP (1-10 sessions) and seven patients (47%) had subsequent FSGS recurrence. Among the 19 DD patients, four received preemptive PP and 12 (63%) had FSGS recurrence. The number of preemptive PP did not affect the recurrence rate. In a group of patients with a previous graft loss secondary to recurrence, the rate of recurrence was lower than expected (40%) and two of the three patients who did not recur had three or more sessions of preemptive PP. Of the 19 patients with recurrence, 17 were treated with PP therapy and 88% of the patients fully or partially responded. Only five patients had graft loss at three yr post-transplant: two from FSGS recurrence and three from non-compliance. These results suggest that preemptive PP does not decrease the rate of recurrence after transplantation but might be beneficial in treating high-risk patients with documented recurrence. Patients with FSGS recurrence post-transplant can achieve good graft survival with both LD and DD transplantation.

Interleukin 7 receptor gene polymorphisms and haplotypes are associated with susceptibility to IgA nephropathy in Korean children

An abnormal T-cell response is involved in the pathogenesis of various renal diseases. Survival of naïve T cells is dependent on interleukin 7 (IL7) and its receptor (IL7R). Thus, we investigated the association between IL7R single nucleotide polymorphisms (SNPs) and childhood IgA nephropathy (IgAN). We analyzed the genotypic distributions of two missense SNPs of IL7R, rs1494558 (Ile66Thr) and rs1494555 (Val138Ile), among 198 pediatric IgAN patients and 288 healthy controls. Haplotype analysis and measurement of pair-wise linkage disequilibrium were performed. In addition, the genotypes of patient subgroups, determined by the presence of nephrotic range proteinuria (>40 mg/m(2)/h) and pathological advancement, were analyzed. The genotyping data of IgAN patients and controls showed significant differences in rs1494558 (codominant, P=0.0003; dominant, P=0.0003) and rs1494555 (codominant, P=0.0038; dominant, P=0.0099). In the haplotype analysis, AC (codominant, P=0.0066) and GT (codominant, P=0.0005; dominant, P=0.0006) were significantly associated with susceptibility to IgAN. Furthermore, in the analysis of clinical subgroups of IgAN patients, rs1494558 was associated with nephrotic range proteinuria (codominant, P=0.027; recessive, P=0.023). Our results suggest that IL7R may be associated with disease susceptibility and proteinuria in childhood IgAN.

Polymorphisms of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) contribute to pathologic progression in childhood IgA nephropathy

Previous studies have suggested that insulin-like growth factor-1 (IGF-1) signaling might play an important role in renal fibrosis and regulation of the proliferation of mesangial cells and podocytes. We conducted the present study to investigate association between single nucleotide polymorphisms (SNPs) of IGF-1 (IGF-1) and IGF-1 receptor (IGF-1R) genes and childhood immunoglobulin (Ig) A nephropathy (IgAN). We analyzed five SNPs of IGF-1 and IGF-1R in 188 pediatric IgAN patients and in 263 healthy controls. We compared variations in SNPs in several sets of IgAN subgroups that were designated based on the presence of nephrotic range proteinuria (>40 mg/m2 per h), podocyte foot process effacement, and pathological progression. Genotyping of IgAN patients and controls revealed differences in IGF-1R rs2229765. Moreover, the rs2195239, rs978458, and rs1520220 SNPs of IGF-1 showed significant association with pathological progression. Thus, in the present study, we observed associations between the IGF-1/1R pathway, susceptibility to IgAN, and the pathologic progression of IgAN.

Renin–angiotensin system gene polymorphisms: association with susceptibility to Henoch–Schonlein purpura and renal involvement

The clinical course of Henoch-Schönlein Purpura (HSP) in children is variable, with some patients having a much more rapidly progressing course than others. We investigated whether polymorphisms of the renin-angiotensin system (RAS) genes are involved in HSP. Three RAS genotypes were examined in 114 children with HSP and in 164 healthy children: the angiotensin I converting enzyme (ACE) insertion/deletion polymorphism, the M235T mutation in the angiotensinogen gene (Agt), and the A1166C in the angiotensin II type I receptor (AT1R) gene. Significant differences were observed between HSP patients and control group in the frequency of ACE and Agt genotypes (p=0.004 and p=0.003, respectively). The TT genotype of Agt gene was associated with a 3.5-fold increased risk for Henoch-Schönlein nephritis (HSN) compared with the MM/MT genotype (odds ratio, 3.5; 95% confidence interval, 1.2-10.4). There was a trend to a higher prevalence of the TT genotype of the Agt gene among patients with nephrotic range proteinuria when compared to the patients with mild proteinuria, although the difference did not reach a statistical significance. The results of this study suggest that polymorphisms of ACE gene and Agt gene likely influence the risk of developing HSP. However, among the three genes of the RAS studies, only Agt gene was associated with the susceptibility to HSN. RAS gene polymorphisms studied are not associated with the presence of nephrotic range proteinuria. Additional studies are warranted to verify the correlation between RAS gene polymorphisms and susceptibility to HSP.

Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy

PurposeHuman immunodeficiency virus (HIV)-associated nephropathy is a common and serious cause of progressive renal insufficiency in patients with HIV, frequently presenting with nephrotic range proteinuria. The purpose of this study is to document the histopathologic diagnoses seen in HIV-positive patients with and without nephrotic range proteinuria and to evaluate the predictive value of both nephrotic range proteinuria and CD4 count in diagnosing HIV-associated nephropathy. MethodsWe performed a cross-sectional, single-center study of all 107 HIV-positive patients who had both a renal biopsy and urine protein measurement between 1995 and 2002. Nephrotic range proteinuria was defined as a urine protein-to-creatinine ratio > 3 or a 24-hour urine protein > 3 g. Clinical and laboratory characteristics of those patients with and without HIV-associated nephropathy were compared. Sensitivity, specificity, and positive and negative predictive values of nephrotic range proteinuria in the diagnosis of HIV-associated nephropathy were determined. ResultsFifty-five biopsied patients had nephrotic range proteinuria, among whom 29 (53%) were diagnosed with HIV-associated nephropathy. Among the remaining patients, 12 had non-HIV-associated nephropathy focal segmental glomeruloscerlosis, 3 had membranoproliferative glomerulonephritis, 2 had AA Amyloid, 2 had diabetic nephropathy, and 7 had other diagnoses. Sensitivity, specificity, and positive and negative predictive values of nephrotic proteinuria in the diagnosis of HIV-associated nephropathy were 73%, 61%, 53%, and 79%, respectively. The patients with HIV-associated nephropathy had a significantly higher creatinine (8.2 mg/dL vs 2.5 mg/dL, P < .001) and a lower CD4 count (158 count/mm3 vs 349 count/mm3, P < .01) at the time of biopsy. Although significantly more patients with HIV-associated nephropathy had a CD4 count below 200 (P = .03), among those with a CD4 count below 200, 10 of 30 patients (33%) had diagnoses other than HIV-associated nephropathy. Injection drug use, presence of hepatitis C, and hypertension were not associated with HIV-associated nephropathy. ConclusionOur results suggest that HIV patients with nephrotic range proteinuria warrant a kidney biopsy because the presence of nephrotic range proteinuria, even in the presence a low CD4 count, does not establish the diagnosis of HIV-associated nephropathy.

Acute Postinfectious Crescentic Glomerulonephritis: Clinicopathologic Presentation and Risk Factors

Glomerular crescent formation is a feature of the most severe forms of human glomerulonephritis. The postinfectious form of rapidly progressive glomerulonephritis with crescents is a form of immune complex glomerulonephritis which seem to have a better prognosis. A relatively poorer prognosis for crescentic postinfectious glomerulonephritis in South Africa has been reported. In the present study, we have tried to determine the mode of presentation, and the prognostic factors for renal and patient outcome for cases with postinfectious crescentic glomerulonephritis (CGN). Between 1990 and 2000 a total number of 128 patients with CGN were managed at our center, among them 23 cases were diagnosed as postinfectious CGN. They were followed-up for a mean period of 40.1 +/- 28.9 months. Among them 12 were males and 11 were females. The median age was 12.35 years (range 4-55 years). The median serum creatinine at presentation was 7.24 mg/dl (range 1.3-14.5 mg/dl). We studied the clinical, laboratory and histopathological data .of our cases and their impact on the renal and patient outcome. By univariate study the risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors. The risk factors that significantly affected patient mortality were hypertension and serum creatinine at last follow-up. postinfectious CGN is a severe form of glomerulonephritis that usually presents with rapidly progressive renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction.

Nephrotic Proteinuria as a Result of Essential Hypertension

Background: The presence of nephrotic-range proteinuria in a nondiabetic hypertensive patient is generally indicative of an underlying glomerular disease. A few published reports have noted nephrotic proteinuria in some patients with hypertensive nephrosclerosis. The frequency of this association is unknown. Methods: We retrospectively reviewed renal biopsy reports on all cases of nephrotic syndrome over an 8-year period (1993–2000). We excluded all cases of diabetes mellitus, lupus, hepatitis, human immunodeficiency virus, and chronic use of nonsteroidal anti-inflammatory drugs. Biopsy specimens showing glomerular eosinophilic hyalinosis lesions, positive immunofluorescence staining, or dense deposits on electron microscopy were also excluded. Thirteen of the remaining 237 (5.5%) biopsy specimens satisfied the standard histological criteria for hypertensive nephrosclerosis. Results: All patients were African-Americans with a mean age of 47.5 ± 13 years and an average mean arterial blood pressure of 122 ± 19 mm Hg. The mean values for urinary protein excretion, serum creatinine, albumin, and cholesterol were 8.9 g/day, 3.3 mg/dl, 3.1 g/dl, and 245 mg/dl, respectively. Optimal blood pressure control required at least three antihypertensive agents. Progression to end-stage renal disease occurred over a mean duration of 8.3 ± 6.5 months. Multivariate regression showed a strong but nonsignificant association between the level of proteinuria at the time of biopsy, duration of hypertension, and number of blood pressure medications (R² = 0.56, p = 0.38). Conclusions: Nephrotic syndrome may be more common in poorly controlled essential hypertension than previously realized. In African-American patients, the differential diagnosis of nephrotic syndrome should include hypertensive nephrosclerosis, but abrogation of renal biopsy is not implied.