IgA Nephropathy with Crescents: A Single-Center Experience.

INTRODUCTION: The presence of crescents in IgA nephropathy (IgAN) has been associated with a poor prognosis. We assess the prognosis of crescents in our patients with IgAN. METHODS: IgAN was diagnosed in 73 patients biopsied at Rush University Medical Center from 1992 to 2020, and crescents were seen in 26 (36%). Clinical, laboratory and histologic features at biopsy, and treatment and outcome (end-stage kidney disease, ESKD) were collected retrospectively. Data are presented as mean ± SD and a p value of <0.05 was significant. RESULTS: There was no difference in hypertension, SCr, or eGFR in patients with crescents compared to those without crescents but patients with crescents had higher UPro/Cr ratio (2.8 ± 2.7 vs. 1.7 ± 1.7 g/g, p 0.04). The percentage of glomeruli with global and segmental sclerosis (32 ± 25% vs. 38 ± 28%, p 0.35) and the proportion of interstitial fibrosis and tubular atrophy (22 ± 20% vs. 22 ± 22%, p 0.76) were similar. Only 19% of patients with crescents had lesions involving ≥25% of glomeruli. A larger proportion of patients with crescents were treated with immunosuppressive agents (70% vs. 21%, p 0.0005). After 8.4 ± 7 years of follow-up, ESKD (19% vs. 23%, p 0.77) and renal survival at 10 years (80% vs. 74%, p 0.99) were similar in patients with and without crescents. CONCLUSION: The presence of crescents in IgAN was not associated with an increased risk of progression to ESKD. This may be a result of the fact that the majority of our patients had crescents involving <25% of glomeruli and received aggressive treatment with immunosuppressive agents.

Percutaneous Renal Biopsy Using an 18-Gauge Automated Needle Is Not Optimal.

BACKGROUND: As percutaneous renal biopsies (PRBs) are increasingly performed by radiologists, an increase in the use of 18-gauge automated needle stands to compromise adequacy. We compare the adequacy and safety of PRB with 14-, 16-, and 18-gauge automated needles. METHODS: PRB of native (N-592) and transplant (T-1,023) kidneys was performed from January 2002 to December 2019 using real-time ultrasound. Baseline clinical and laboratory data, biopsy data (number of cores, total glomeruli, and total glomeruli per core), and outcome (hematoma on renal US at 1-h, complications, and transfusion) were collected prospectively. PRB with N14g (337) versus N16g (255) and T16g (892) versus T18g (131) needles were compared. A p value of <0.05 was significant. RESULTS: PRB with an 18-g needle yielded the lowest number of total glomeruli per biopsy (N14g vs. N16g: 33 ± 13 vs. 29 ± 12, p < 0.01 and T16g vs. T18g: 34 ± 16 vs. 21 ± 11, p < 0.0001), significantly fewer total glomeruli per core (T16g vs. T18g: 12.7 ± 6.4 vs. 9.6 ± 5.0, p < 0.001 and N16g vs. T18g: 14.2 ± 6.3 vs. 9.6 ± 5.0, p < 0.001). A hematoma by renal US 1-h post-PRB was similar for native (14g-35% vs. 16g-29%, p = 0.2), and transplant biopsies (16g-10% vs. 18g-9%, p = 0.9) and the complication rate for native (14g-8.9% vs. 16g-7.1%, p = 0.5), transplant biopsies (16g-4.6% vs. 18g-1.5%, p = 0.2) and transfusion rate for native (14g-7.7% vs. 16g-5.8%, p = 0.4), and transplant biopsies (16g-3.8% vs. 18g-0.8%, p = 0.1) were similar irrespective of needle size. CONCLUSIONS: PRB of native and transplant kidneys with the use of a 16-gauge needle provides an optimal sample. However, our experience in transplant biopsies suggests the use of an 18-gauge needle stands to jeopardize the diagnostic accuracy of the PRB while not improving safety.

Changing Trends in the Performance of Percutaneous Renal Biopsy from Nephrologist to Interventional Radiologist: A Single-Center Experience.

BACKGROUND: Percutaneous renal biopsy of native kidneys (PRB) has been an integral part of the practice of nephrology. However, over the past 30 years, PRB has transitioned from a procedure performed only by nephrologists to interventional radiologists (IRs). We surveyed practicing nephrologists completing training in our program to determine the clinical practice patterns of PRB. METHODS: The 78 fellows completing the nephrology program at Rush University Medical Center from June 1984 through June 2017 were successfully contacted and surveyed regarding their opinion on adequacy of their training and whether they performed PRB in practice and if not or no longer, why. To evaluate for differences in the performance of PRB over time, a comparison of 4 periods of fellowship completion (i.e., 1984-1990, 1991-2000, 2001-2010, 2011-2017) was performed. RESULTS: All 78 nephrologists felt they had been adequately trained to perform PRB. PRB was performed by 45 (58%) nephrologists post-fellowship, but a significant decline was observed over the 4 periods of time from 1984 to 2017 (100 vs. 86 vs. 52 vs. 20%, p < 0.0001). The primary reason that 33 nephrologists did not perform PRB was that it was too time consuming and IR was available to perform PRB. Of the 71 nephrologists still in practice only 12 (17%) continue to perform PRB. A greater proportion of nephrologists completing training from 1984-1990 continue to perform PRB relative to those trained after 1990. The universal reason that nephrologists were no longer performing PRB was again an issue of time and the fact that IRs were available to perform PRB. CONCLUSION: We find that there has been a significant transition over time in the performance of PRB by a nephrologist to IR. The major reason for this is the time burden associated with PRB and the availability of IRs.

Adequacy and complication rates with 14- vs. 16-gauge automated needles in percutaneous renal biopsy of native kidneys.

In performing percutaneous renal biopsy (PRB) of native kidneys, an increasing use of 16-gauge automated biopsy needles has been observed. We compare the adequacy and safety of PRBs in adults performed with a 14-gauge (n = 82) vs. 16-gauge (n = 55) automated needle using real-time ultrasound (US) from 1/2010 to 12/2013. Baseline clinical and laboratory data along with outcome data (renal US 1-hour postbiopsy, biopsy adequacy, and safety) were collected prospectively. There was no difference in age, gender, blood pressure, serum creatinine, or pre-PRB hemoglobin at baseline for PRBs performed with a 14- vs. 16-gauge needle. The number of glomeruli obtained per biopsy was similar (29 ± 11 vs. 31 ± 14, p = 0.6) and adequate tissue for diagnosis was obtained in 99% and 100% of biopsies. The clinical complication (8.5% vs. 9.1%, p = 1.0), transfusion (7.3% vs. 7.2%, p = 1.0), and embolization (3.7% vs. 1.8%, p = 0.6) rates were not significantly different for 14- vs. 16-gauge needles, but by routine renal US 1-hour post-PRB, a perinephric hematoma was demonstrated more often in biopsies done with the 14-gauge needle (39% vs. 22%, P 0.04). Thus, while the success of PRB of native kidneys is similar for both needle gauges, the potential for complication may be less using a 16-gauge automated needle.

Percutaneous renal biopsy of native kidneys: a single-center experience of 1,055 biopsies.

BACKGROUND: Percutaneous renal biopsy (PRB) of native kidneys is an essential tool in the diagnosis and management of renal disease. We report one of the largest single-center experiences on the success and safety of the procedure. METHODS: From June 1983 to March 2012, 1,055 adults underwent PRB using real-time ultrasound guidance and 14-gauge biopsy needles. Data were collected prospectively for 826 biopsies (78%). Statistical analysis was performed using the Mann-Whitney test, Wilcoxon matched pairs test and Kruskal-Wallis test for continuous data or the Fisher's exact test and χ(2) test for categorical data. Multivariate analysis using logistic regression was performed to determine which feature at baseline was predictive of a complication following renal biopsy. RESULTS: Patients were aged 46 ± 17 years; 38% were male, 40% were white and 43% were African-American. Serum creatinine (SCr) was 2.3 ± 2.3 mg/dl (>1.5 mg/dl in 47%). The pre-PRB hemoglobin was 12 ± 2 g/dl (<11.0 g/dl in 35%). Adequate tissue for diagnosis was obtained in 99% of biopsies. Minor complications occurred in 8.1% of biopsies (mainly gross hematuria, in 4.5%). Major complications occurred in 6.6% of biopsies, with transfusions required in 5.3%. Only 1 death (0.09%) resulted from post-PRB bleeding. By multivariate analysis, baseline features predictive of a complication were systolic blood pressure >170 mm Hg (OR 4.2, 95% CI 1.8-9.8), bleeding time >7.5 min (OR 1.7, CI 1.2-2.5) and SCr >3.5 mg/dl (OR 1.8, CI 1.2-2.9). CONCLUSIONS: PRB of native kidneys using real-time ultrasound with a 14-gauge automated needle remains a successful and safe procedure.

Severe lupus nephritis: the predictive value of a ≥ 50% reduction in proteinuria at 6 months.

BACKGROUND: A complete remission (CR) in severe lupus nephritis (SLN) is associated with a favorable long-term outcome. Initial therapy may be up to 6 months, but many patients do not achieve a CR until after 12 months. We assess the value of a ≥50% reduction in proteinuria (UPro) at 6 months in predicting the outcome in SLN patients. METHODS: We evaluated the 86 adult patients in the prospective, controlled trial of plasmapheresis (PP) in SLN (NEJM 1992). Patients with a CR (n = 12), end-stage renal disease (ESRD) or death (n = 13) at ≤6 months were excluded. The remaining 61 patients were categorized into two groups based on having attained a ≥50% reduction in UPro at 6 months: (yes) 34 patients and (no) 27 patients. The long-term outcomes were compared. A CR was defined by a serum creatinine (SCr) of ≤1.4 mg/dL and UPro of ≤0.33 g/day. RESULTS: Baseline features were similar, but the UPro was higher (7.1 ± 3.6 versus 4.6 ± 3.2, P 0.002) in the group with a ≥50% reduction in UPro at 6 months. At follow-up, a CR was attained in 56% of patients with a ≥50% reduction in UPro at 6 months compared with 22% (P = 0.009) in the group without. The 15-year renal survival (71 versus 25%, P = 0.005) and patient survival without ESRD (66 versus 18%, P = 0.004) was greatest in the patients with a ≥50% reduction in UPro at 6 months. CONCLUSION: A ≥50% reduction in UPro at 6 months predicts a favorable outcome in SLN.

Treatment of primary FSGS in adults.

Over the last 20 years, primary FSGS has emerged as one of the leading causes of idiopathic nephrotic syndrome in adults, particularly among African Americans. In nephrotic patients, progression to ESRD often occurs over the course of 5-10 years, whereas non-nephrotic patients and those entering a remission have an extremely favorable prognosis. As a result, it is in patients who remain persistently nephrotic despite conservative therapy that a more aggressive therapeutic approach is taken. Primary FSGS was once considered an entity nonresponsive to prednisone or immunosuppressive agents, but it has become apparent over the last 20 years that a substantial portion of nephrotic adults with primary FSGS do respond to treatment with a significantly improved prognosis. The recent histologic classification proposed for FSGS has provided additional insights into the prognosis and response to therapy. This article reviews the current knowledge regarding the presentation, prognosis, and therapeutic approach in adults with primary FSGS.

Bartonella henselae Infective Endocarditis: A Rare Cause of Pauci-Immune Necrotizing Glomerulonephritis-A Case Report.

Rationale: Bartonella sp. are the most common causes of culture-negative infective endocarditis (IE) cases in the United States. Although, infection-related glomerulonephritis can frequently mimic primary vasculitis due to pauci-immune pattern, majority of previously reported cases of Bartonella henselae-associated glomerulonephritis have immune-complex deposits on immunofluorescence. We present a rare case of B henselae IE-related pauci-immune necrotizing glomerulonephritis. Timely recognition of this atypical presentation led to appropriately directed medical therapy. Presenting concerns of the patient: A 33-year-old Caucasian male with a history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART), alcohol abuse, previous subarachnoid hemorrhage (SAH), and recent wisdom tooth extraction (on amoxicillin) was transferred from an outside hospital for further evaluation of severe headache. He was diagnosed with an SAH and right anterior cerebral artery mycotic aneurysm. The serum creatinine at the outside hospital was 292 umol/L (3.3 mg/dL) with a previously normal baseline around 2 years ago. The serum creatinine at our institution was 256 umol/L (3.0 mg/dL). The urinalysis demonstrated +100 protein, +3 blood and 29 red blood cells/high power field. The urine protein creatinine ratio (UPC) was 1.7 g/g. Serologic evaluation was positive for a low C4 10.2 mg/dL, elevated rheumatoid factor 40 IU/mL and an elevated proteinase 3 (PR-3) antineutrophilic cytoplasmic antibodies (ANCA Ab) 4.0 U/mL. A transesophageal echocardiogram (TEE) showed echo densities on both mitral and aortic valve. Blood cultures were negative. Further serologic evaluation was positive for B henselae IgG titer of 1:2560 (normal <1:320) with a negative IgM titer. Diagnoses: A percutaneous kidney biopsy revealed pauci-immune necrotizing glomerulonephritis, with 14/16 glomeruli globally sclerotic, and 2 glomeruli with active segmental necrotizing lesions. There was no evidence of immune-complex deposition on immunofluorescence or electron microscopy. Clinical findings were consistent with B henselae IE associated mycotic aneurysm and necrotizing glomerulonephritis. Intervention: Empiric treatment for an active glomerulonephritis with immunosuppressive agents was deferred on admission, given concern for an underlying infectious process and mycotic aneurysms in an HIV-positive patient. He received antibiotic treatment with doxycycline and ceftriaxone with gentamicin for synergy. Despite this, the mitral and aortic valve regurgitation worsened, and he developed congestive heart failure requiring aortic valve replacement and mitral valve repair. The explanted aortic valve was positive for B henselae by polymerase chain reaction (PCR) confirming the diagnosis of B henselae IE. Outcomes: Immunosuppression was deferred due to timely identification of an atypical presentation of B henselae-associated ANCA antibodies-positive, pauci-immune necrotizing glomerulonephritis. A course of antibiotic treatment resulted in improved renal functions along with undetectable B henselae and PR3 Ab titers. The serum creatinine decreased to 176 umol/L (2 mg/dL) and remained stable 12 months after discharge. Teaching points: B henselae IE should be suspected in patients with pauci-immune necrotizing glomerulonephritis and culture-negative IE. This is imperative for optimal decision making in the management of such patients. Having high clinical suspicion can avoid unnecessary and potentially deleterious use of immunosuppressive agents.

Justification: La bactérie Bartonella sp est la cause la plus fréquente des cas d'endocardite infectieuse (EI) à culture négative aux États-Unis. Bien qu'il arrive souvent que les glomérulonéphrites, en raison de leur schéma auto-immun, puissent ressembler à des vascularites primaires, la majorité des cas précédemment signalés de glomérulonéphrites associées à B. henselae présentent des dépôts de complexes immuns sur immunofluorescence. Nous présentons un cas rare d'endocardite infectieuse à B. henselae associée à une glomérulonéphrite pauci-immune nécrosante. La reconnaissance rapide de cette présentation atypique a conduit à un traitement médical bien dirigé. Présentation du cas: Un homme caucasien de 33 ans atteints du virus de l'immunodéficience humaine (VIH) sous traitement antirétroviral hautement actif (HAART) qui avait été transféré d'un autre hôpital pour une évaluation plus approfondie de céphalées intenses. Le patient avait des antécédents d'abus d'alcool, d'une hémorragie sous-arachnoïdienne (HSA) antérieure et d'une récente extraction de dents de sagesse (prise d'amoxicilline). Le patient a reçu un diagnostic d'HSA et d'anévrisme mycotique de l'artère cérébrale antérieure droite. Le taux de créatinine sérique mesuré à l'hôpital externe était de 292 umol/L (3,3 mg/dL); le patient présentait une valeur normale environ 2 ans auparavant. Le taux de créatinine sérique mesuré dans notre établissement était de 256 umol/L (3,0 mg/dL). L'analyze d'urine a révélé un décompte supérieur à 100 pour les protéines et de + 3 pour le sang avec 29 globules rouges/champ à puissance élevée. Le rapport protéine/créatinine urinaire (UPC) était de 1,7 g/g. L'évaluation sérologique était positive pour un faible taux de C4 (10,2 mg/dL), un taux élevé de facteur rhumatoïde (40 UI/mL) et un taux élevé (4,0 U/mL) d'anticorps anti-cytoplasme des neutrophiles (ANCA) anti-protéinase 3 (PR-3). Une échocardiographie transœsophagienne (ÉTO) a montré des végétations sur les valves mitrale et aortique. Les hémocultures étaient négatives. Une évaluation sérologique plus poussée s'est avérée positive pour le titer d'IgG de B. henselae, avec un rapport de 1:2560 (normale = inférieur à 1:320), et négative pour le titer d'IgM. Diagnostics: Une biopsie rénale percutanée a révélé une glomérulonéphrite pauci-immune nécrosante avec un taux de 14/16 glomérules sclérotiques et 2 glomérules présentant des lésions segmentaires nécrosantes actives. Aucune preuve de dépôt de complexe immun n'a été observée par immunofluorescence ou par microscopie électronique. Les résultats cliniques correspondaient à une endocardite infectieuse à B. henselae associée à l'anévrisme mycotique et à la glomérulonéphrite nécrosante. Intervention: Le traitement empirique d'une glomérulonéphrite active avec des agents immunosuppresseurs a été reporté lors de l'admission, en raison de la crainte d'un processus infectieux sous-jacent et d'anévrismes mycotiques chez un patient séropositif. Le patient a reçu un traitement antibiotique de doxycycline et de ceftriaxone avec gentamicine pour la synergie. Malgré cette intervention, la régurgitation des valves mitrale et aortique s'est aggravée et le patient a développé une insuffisance cardiaque congestive qui a nécessité le remplacement de la valve aortique et la réparation de la valve mitrale. Une analyze par PCR (réaction en chaîne de la polymérase) sur la valve aortique explantée s'est avérée positive pour B. henselae, ce qui a confirmé le diagnostic d'endocardite infectieuse à B. henselae. Résultats: Le traitement immunosuppresseur a été reporté en raison de l'identification opportune d'une présentation atypique de glomérulonéphrite pauci-immune nécrosante positive pour les anticorps anti-cytoplasme des neutrophiles (ANCA) associés à B. henselae. Un traitement antibiotique a permis d'améliorer la fonction rénale et a ramené les titres de B. henselae et d'Ac PR3 à des niveaux indétectables. Le taux de créatinine sérique est passé à 176 umol/L (2 mg/dL) et est demeuré stable 12 mois après le congé du patient. Enseignements tirés: L'endocardite infectieuse associée à B. henselae doit être suspectée chez les patients atteints d'une glomérulonéphrite pauci-immune nécrosante et d'une endocardite infectieuse à culture négative. Ceci est impératif afin d'assurer une prise de décision optimale pour la prise en charge de ces patients. Dans ce cas particulier, une suspicion clinique importante peut prévenir l'utilization inutile et potentiellement délétère d'agents immunosuppresseurs.

Complete remission in severe lupus nephritis: assessing the rate of loss in proteinuria.

BACKGROUND: The prognosis of severe lupus nephritis (SLN) is improved in patients attaining a complete remission (CR). The time to remission ranges from 10 to 16 months with many patients not attaining a CR until after 12 months. We assessed whether the rate of loss in proteinuria (UPro) is predictive of a CR in SLN patients. METHODS: We studied 85 adult patients in the prospective controlled trial of plasmapheresis in SLN (New England Journal of Medicine 1992). All patients had International Society of Nephrology/Renal Pathology Society Class IV±Class V lesions. All patients received prednisone and oral cyclophosphamide and 39 patients received plasmapheresis. A CR was defined by a serum creatinine (SCr) of ≤1.4 mg/dL and UPro of ≤0.33 g/day. The change in UPro in gram per day per week was determined at 3 and 6 months from entry to the study. RESULTS: A CR was attained in 37 patients (44%) by 16±14 months. The level of UPro at baseline was similar in CR and no remission (NR) patients (5.5 versus 6.4 g/day), but CR patients had a lower SCr (1.2 versus 2.4, P<0.0001). At 6 months, the rate of change of UPro was higher at (-)0.224 g/day/week in CR patients and (-)0.107 g/day/week in NR patients (P=0.01) and a 50% reduction in UPro was seen in 78% of CR patients but only 42% of NR patients (P=0.009). The time to a CR was ≤12 months in 19 patients and >12 months in 18 patients. The baseline SCr was similar among the two groups. However, UPro at baseline was lower in patients with CR in ≤12 months (3.9±2.7 versus 7.2±3.0 g/day, P=0.001) but the proportion of patients with membranous glomerulonephritis was similar (16 versus 22%). The rate of change in UPro at 6 months was similar at (-)0.214 g/day/week in patients with CR ≤12 months and (-)0.235 g/day/week in those with CR>12 months (P=0.6). At 6 months, a 50% reduction in UPro was also similar in the two groups (84 versus 72%, P=0.4). Additionally, the rate of change in UPro at 3 and 6 months was similar within each group. CONCLUSIONS: The rate of change in proteinuria at 6 months is significantly greater in patients attaining a CR relative to NR patients but similar in patients with a CR in ≤12 months or >12 months. Thus, the rate of loss of UPro at 6 months may help in predicting which patients will attain a CR.

The safety and tolerability of ferric citrate as a phosphate binder in dialysis patients.

BACKGROUND: A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. METHODS: Enrollment occurred in two periods. Period 1 recruited patients taking 6-15 pills/day of binder with phosphorus of ≥2.5 mg/dl. Period 2 recruited patients taking ≥12 pills/day of binder with phosphorus of ≥3.5 mg/dl. Participants with ferritin ≥1,000 µg/l or transferrin iron saturation (TSAT) ≥50% at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5-5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was <500 µg/l and TSAT <30%. RESULTS: Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69%), constipation (15%), and bloating (7%). Mean iron parameters at the beginning of the study were ferritin 554 ± 296 µg/l, iron 68 ± 21 µg/dl, and iron saturation 30 ± 7.8%. At the end of study, mean ferritin was 609 ± 340 µg/l (p = 0.02), iron 75 ± 27 µg/dl (p = 0.04), and TSAT was 35 ± 13% (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. CONCLUSION: Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.

APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.

Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.

The Oxford classification of IgA nephropathy: a retrospective analysis.

BACKGROUND/AIMS: The Oxford classification of IgA nephropathy (IgAN) assesses the presence of mesangial hypercellularity ≥50% (M1 vs. 0), endocapillary proliferation (E1 vs. 0), segmental glomerulosclerosis (S1 vs. 0), tubular atrophy/interstitial fibrosis >25 or 50% (T1 or 2 vs. 0), and has been reported as having prognostic value. We studied the clinical significance of the classification in our adult patients with IgAN. METHODS: Retrospective study of 54 patients with biopsy-proven IgAN seen from 1983 to 2009. The correlation between the Oxford classification and baseline renal function was assessed. The primary endpoint was a 50% reduction in eGFR or end-stage renal disease. Predictors for progression to the endpoint were determined by multivariate analyses. RESULTS: Patients were 41 ± 15 years of age with a serum creatinine of 1.5 ± 0.8 mg/dl, eGFR of 61 ± 24 ml/min/1.73 m(2), and proteinuria of 2.0 ± 1.6 g/day. Oxford classifications were as follows: M1 = 72%, E1 = 20%, S1 = 81%, and T1 = 13%/T2 = 22%. During the follow-up of 5.8 ± 4.8 years, 19% of patients reached the primary endpoint. While the Oxford classification was associated with progressive renal disease, only the T score (T0, T1, T2) was predictive of outcome with 6, 29, and 50% of patients (p = 0.002) reaching the primary endpoint. The 10-year renal survival for T0, T1, and T2 was 100, 50, and 17%, respectively (p < 0.001). By multivariate analysis, the hazard ratio for reaching the primary endpoint was 32 for patients with T ≥1 versus T0 (p = 0.01). CONCLUSIONS: In our experience, the Oxford classification predicts progressive renal disease, but the degree of tubulointerstitial fibrosis was the only feature independently predictive of outcome.

Pruritic rash and eosinophilia in a patient receiving peritoneal dialysis.

A 28-year-old woman with end-stage renal disease maintained on peritoneal dialysis developed a hyperpigmented macular pruritic rash on multiple parts of her body associated with an eosinophilia of 22%. The consulting allergist suspected a silicone allergy from the peritoneal dialysis catheter. A patch test confirmed this diagnosis. Treatment with both topical and systemic steroids was ineffective. Following a living nonrelated renal transplant and removal of the catheter the rash and eosinophilia resolved.

Pathogenetic features of severe segmental lupus nephritis.

BACKGROUND: Accumulating evidence supports the notion that the pathogenesis of severe lupus glomerulonephritis is multifactorial and not solely an immune complex-mediated glomerular disease. Alternate mechanisms for glomerular destruction may exist. METHODS: We conducted a retrospective clinicopathologic analysis of 213 patients with lupus nephritis. Twenty-six patients had severe segmental glomerulonephritis (SSGN) and 15 patients had diffuse proliferative glomerulonephritis (DPGN). Patients with pure mesangial lupus nephritis [mesangial glomerulonephritis (MesGN)] (N = 13) were used as histologic controls. The degree of immunologic activity detailed by histologic data including light, fluorescent (IF) and electron microscopy (EM) on kidney biopsies and clinical data from patients with severe lupus nephritis were analysed. RESULTS: Biopsies from patients with SSGN had fewer glomeruli with wire loops (3 +/- 6% versus 35 +/- 34% P = 0.005) and hyaline thrombi (0.8 +/- 3% versus 16 +/- 22%, P = 0.02) compared to DPGN. The amount of IgG by IF was less in SSGN lesions compared to DPGN lesions, and IgG was absent in 30% of the SSGN group compared to none of the DPGN group (P = 0.04). There was no difference in mesangial deposits among the three groups (SSGN, DPGN and MesGN). The EM data supported the IF data. Anti-neutrophil cytoplasmic antibodies (ANCA) were essentially negative in all three groups and the C3 values tended to be lower in DPGN compared to SSGN (48 +/- 15 mg/dl versus 60 +/- 26 mg/dl, P = 0.09). CONCLUSIONS: The findings in DPGN involve a classic immune complex-mediated glomerulonephritis as demonstrated by the abundant immune aggregates witnessed in the peripheral capillary wall. In contrast, a paucity of peripheral immune aggregates is seen in SSGN implying a different pathogenesis. Our data support a mechanism of glomerular injury in SSGN that is separate from the generally accepted unitary concept of immune complex deposition in lupus nephritis.

The value of post-biopsy ultrasound in predicting complications after percutaneous renal biopsy of native kidneys.

BACKGROUND: Clinically significant bleeding complications occur in >30% of patients undergoing percutaneous renal biopsy (PRB) of native kidneys and can be severe in up to 10% of patients. A noninvasive measure that would reliably predict which patients will do well with an uncomplicated post-biopsy course or which patients may be at risk of developing a clinically significant complication is in great demand. METHODS: PRB of native kidneys was performed in 162 adult patients from February 2002 through February 2007 using real-time ultrasound and automated needle. Renal ultrasound (US) was performed at 1-h post-PRB to assess biopsy-related bleeding. Patients were observed for 24 h post-PRB to monitor clinically apparent biopsy-related complications. The value of the post-biopsy ultrasound in predicting complications was assessed. RESULTS: A clinically apparent complication was observed in 26 (16%) patients post-PRB (13 minor not requiring any intervention and 13 major requiring intervention). In patients with complicated courses, a haematoma at 1 h was seen in 77% (69% with minor and 87% with major complications). However, only 27 (20%) of 136 patients without complications (P < 0.0001) had a haematoma at 1 h. The presence of a haematoma 1-h post-PRB had a sensitivity of 77%, specificity of 80%, positive predictive value of 43% but a negative predictive value of 95% for predicting clinical complications. CONCLUSIONS: We find that with the use of renal ultrasound 1-h post-PRB, the absence of perinephric bleeding is predictive of an uncomplicated course while the presence of a perinephric haematoma is not reliably predictive of a clinically significant complication post-renal biopsy.

Establishing Surrogate Kidney End Points for Lupus Nephritis Clinical Trials: Development and Validation of a Novel Approach to Predict Future Kidney Outcomes.

OBJECTIVE: End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long-term kidney survival. This study was undertaken to identify short-term end points that predict long-term kidney outcomes for use in clinical trials. METHODS: A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long-term outcomes in a 36-month follow-up period. The long-term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. RESULTS: Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction-period CKD status, 12-month proteinuria, and 12-month serum creatinine level. The SKI HIT variables included prediction-period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12-month proteinuria, 12-month serum creatinine level, race, and an interaction between ISN/RPS class and 12-month proteinuria. The RRT HIT included age at diagnosis, 12-month proteinuria, and 12-month serum creatinine level. Each HIT validated well internally (c-indices 0.84-0.92) and in an independent LN cohort (c-indices 0.89-0.92). CONCLUSION: HITs, derived from short-term kidney responses to treatment, correlate with long-term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials.

The prognosis and pathogenesis of severe lupus glomerulonephritis.

BACKGROUND: The International Society of Nephrology/ Renal Pathology Society classification (ISN/RPS) of lupus glomerulonephritis (GN) divides diffuse GN (>/=50% involvement) into diffuse segmental (IV-S) and diffuse global GN (IV-G). This division tests whether the pathogenesis and clinical outcomes are the same as when similar patients are classified using the World Health Organization (WHO) classification into severe segmental (WHO III >/=50%) and diffuse global (WHO-IV) GN. METHODS: Thirty-nine renal biopsies with WHO class IV and 44 with WHO III >/= 50% were reclassified using the ISN/RPS and were correlated with pathogenesis and outcome. RESULTS: There were 22 biopsies with ISN/RPS class IV-S. ISN/RPS class IV-G comprises two morphologically discrete classes of renal biopsies: 39 biopsies originally classified as WHO class IV (WHO-IV) and 22 that switched from WHO III >/=50% to ISN/RPS class IV-G (IV-Q). We will analyze IV-S, IV-Q and WHO-IV separately. WHO-IV had significantly more immune aggregate deposition than IV-S and IV-Q. WHO-IV had lower serum complements C3 (P = 0.05) and C4 (P = 0.05) than patients with IV-Q. Patients with WHO-IV had more remissions (56%) than IV-Q (23%) (P = 0.01), and stable renal function at the last follow-up was less frequent in patients with IV-Q (18%) than IV-S (50%, P = 0.05) and WHO-IV (62%, P = 0.001). Renal survival and renal survival without end-stage renal disease were different when the patients were diagnosed as WHO classes III >/=50% and IV, but the outcomes for ISN/RPS class IV-S and IV-G (WHO-IV plus IV-Q) were not different. CONCLUSIONS: WHO III >/=50% and WHO-IV lupus GN are not congruent with ISN/RPS IV-S and IV-G. The ISN/RPS minimizes pathological and outcome differences between classes IV-S and IV-G which results in the loss of informational content from the renal biopsies. ISN/RPS does not detect pathogenetic or clinical differences among patients with severe lupus GN.

NPHS2 variation in sporadic focal segmental glomerulosclerosis.

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3' untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR = 4.9, P = 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in European-Americans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR = 0.5, P = 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS.