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.

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.

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.

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.

Risk of percutaneous renal biopsy of native kidneys in the evaluation of acute kidney injury.

BACKGROUND: Percutaneous renal biopsy (PRB) of native kidneys (NKs) to better understand and treat acute kidney injury (AKI) is being advocated, but little is known about the risk of complications. METHODS: We performed a retrospective study of PRB of NKs in 955 adults from 1991 to 2015 at an academic medical center with real-time ultrasound and automated biopsy needles. Patients undergoing PRB for evaluation of AKI (n = 160) were compared with 795 patients biopsied for other reasons (not-AKI) for postbiopsy complications [need for transfusion of packed red blood cells (PRBCs), an interventional radiologic or surgical procedure, readmission or death]. RESULTS: Patients biopsied for AKI were older (58 ± 16 versus 44 ± 16 years; P < 0.0001), with a higher serum creatinine (SCr) (4.5 ± 2.7 versus 1.8 ± 1.6 mg/dL; P < 0.0001) and lower hemoglobin (Hgb) (10.4 ± 1.7 versus 12.1 ± 2.1; P < 0.0001) and a greater proportion had an abnormal bleeding time (12.5% versus 7.4%, P 0.04), partial thromboplastin time (15.2% versus 5.3%, P < 0.0001) and/or prothrombin time (27.0% versus 12.8%; P < 0.0001) compared with not-AKI patients. Complications post-PRB were significantly greater in patients biopsied for AKI {11.3% versus 6.7%; P=0.04; odds ratio [OR] 1.78 [95% confidence interval (CI) 1.01-3.12]} with patients biopsied for AKI requiring more blood transfusions (10.0% versus 5.3%; P 0.02; OR 2.04 (95% CI 1.12-3.74)]. By multivariate analysis, baseline features predictive of a complication were increased SCr and decreased Hgb level, as well as female gender and increased systolic blood pressure. CONCLUSION: Patients biopsied for evaluation of AKI are at greater risk of complications due to increased risk factors.

Comparison of native and transplant kidney biopsies: diagnostic yield and complications.

BACKGROUND: The safety and adequacy are established for the native percutaneous renal biopsy (PRB) but no prospective studies exist that directly compare these with transplant PRB. METHODS: From 1995 to 2015, 1705 adults underwent percutaneous native [native renal biopsy (NRB)] or transplant renal biopsy (TRB) by the Nephrology service. Real-time ultrasound and automated biopsy needles (NRB, 14 or 16 gauge; TRB, 16 gauge) were used. Patients were observed for 24 h (NRB) or 8 h (TRB) post-procedure. Adequacy was defined as tissue required for diagnosis plus glomerular yield. Complications were defined as those resulting in the need for an intervention, such as surgery, interventional radiologic procedure, readmission, blood transfusion and death. Data were collected prospectively in all biopsies. RESULTS: At the time of biopsy, NRB patients were younger (mean ± SD, 47 ± 17 versus 50 ± 14 years, P < 0.0001) and more often female (62 versus 48%, P < 0.0001) compared with TRB. A fellow supervised by an attending performed the procedure in 91% of NRB compared with 63% of TRB (P < 0.0001). TRB patients were more hypertensive [systolic blood pressure (SBP) 140 ± 22 versus 133 ± 18 mmHg, P < 0.0001] and had a higher serum creatinine (3.1 ± 1.8 versus 2.3 ± 2.2 mg/dL, P < 0.0001), activated partial thromboplastin time (28 ± 4.3 versus 27 ± 5 s, P < 0.0001) as well as lower hemoglobin (Hgb) (11.2 ± 1.8 versus 11.7 ± 2.1 g/dL, P < 0.0001) compared with NRB. Adequate tissue for diagnosis was obtained in > 99% of NRB and TRB (P = 0.71). Compared with TRB, NRB had a greater drop in Hgb after the biopsy (0.97 ± 1.1 versus 0.73 ± 1.3 g/dL, P < 0.0001), a higher complication rate (6.5 versus 3.9%, P = 0.02) and higher transfusion rate (5.2 versus 3.3%, P = 0.045). There was one death in each group attributed to the biopsy. CONCLUSIONS: Although death is equally rare, the complication rate is higher in NRB compared with TRB despite TRB having more of the traditional risk factors for bleeding. Differences in technique, operator (fellow or attending) or needle gauge may explain this variability.

The Impact of Baseline Serum Creatinine on Complete Remission Rate and Long-Term Outcome in Patients with Severe Lupus Nephritis.

BACKGROUND/AIM: We assess the impact of serum creatinine at baseline on complete remission rate and long-term outcome in severe lupus nephritis (SLN). METHODS: A total of 86 adult patients with SLN [International Society of Nephrology/Renal Pathology Society (ISN/RPS) class IV lesions] were evaluated based on baseline serum creatinine levels (≤1.0, 1.01-1.5, 1.51-2.0, 2.01-3.0, and >3.0 mg/dl; n = 22, 23, 16, 12, and 13, respectively). The complete remission rates (serum creatinine level of ≤1.4 mg/dl and proteinuria of ≤0.33 g/day) and long-term outcomes (stable renal function, dialysis, and death) were compared. The patients were followed for 121 ± 64 months. RESULTS: The baseline clinical features were similar, but the chronicity index was significantly higher with increasing levels of serum creatinine. Complete remission rates were significantly higher in patients with lower levels of serum creatinine (86 vs. 52 vs. 19 vs. 25 vs. 0%, p < 0.0001). Patients with a baseline serum creatinine level of ≤1.0 mg/dl were >16 times as likely (OR 16.2; 95% CI: 4.2-61.5) to attain a complete remission and >6 times as likely (OR 6.1; 95% CI: 1.9-18.6) to have stable renal function at the last follow-up as compared to patients with a serum creatinine level of >1.0 mg/dl. The 15-year renal survival rate was greatest among those patients with a baseline serum creatinine level of ≤1.0 mg/dl (76 vs. 57 vs. 48 vs. 25 vs. 10%, p < 0.0001). CONCLUSION: The prognosis of SLN is significantly affected by the serum creatinine level at baseline. The complete remission rate is highest, and the long-term prognosis most favorable, in patients with a baseline serum creatinine level of ≤1.0 mg/dl. This emphasizes the importance of early diagnosis and treatment.

Clinical factors influencing the decision to transfuse after percutaneous native kidney biopsy.

BACKGROUND: Transfusion of erythrocytes is the most common intervention after a complicated percutaneous renal biopsy (PRB). Anemia is considered to be a leading risk factor for bleeding following a PRB, and based on recent studies of transfusions in hospitalized patients, many institutions are restricting the threshold for erythrocyte transfusion to a lower hemoglobin concentration (Hgb). The purpose of this study is to analyze factors that influence the transfusion decision after a PRB, and to determine whether anemia is truly a risk factor for bleeding or anemic patients are simply more likely to receive a transfusion because of their already lower pre-PRB Hgb. METHODS: PRB of native kidneys was performed using real-time ultrasound with automated biopsy needles from January 1990 to April 2014. All patients were prospectively followed for bleeding with a 24-h inpatient observation. An intervention for a bleeding complication (BL-I) was defined by undergoing a procedure (cystoscopy, embolization), receiving a blood transfusion (BL-T), death and/or readmission related to the biopsy. To further define the effect of anemia, patients were divided into three pre-PRB Hgb groups: <9.0 g/dL (n = 79), 9.0-11.0 g/dL (n = 266) and >11.0 g/dL (n = 565). RESULTS: BL-I occurred in 71/910 (7.8%) of PRBs. The majority of these were BL-T (57/71, 80%; 57/910, 6.3% overall). Patients with BL-I had lower pre-PRB Hgb than those without BL-I (mean ± SD; 10.3 ± 2.0 versus 12.0 ± 2.1 g/dL, P < 0.0001) and a greater change (Δ) in Hgb (2.1 ± 1.6 versus 1.0 ± 0.8 g/dL, P < 0.0001). When compared with higher Hgb, patients with Hgb <9.0 g/dL had more traditional risk factors for bleeding (older age: 49 ± 18 versus 48 ± 18 versus 45 ± 16 years, P = 0.02; female: 72 versus 70 versus 56%, P < 0.0001; higher serum creatinine: 4.0 ± 2.9 versus 2.9 ± 2.6 versus 1.7 ± 1.4 mg/dL, P < 0.0001; higher systolic blood pressure: 138 ± 18 versus 133 ± 19 versus 133 ± 18 mmHg, P = 0.06; higher bleeding time: 7.6 ± 1.8 versus 7.4 ± 2.0 versus 6.7 ± 1.8 min, P < 0.0001). When BL-T was stratified by pre-PRB Hgb, there were more transfusions in those with lower pre-PRB Hgb (24 versus 9 versus 3%, P < 0.0001). However, these patients not only had fewer hematomas (58 versus 83 versus 87%, P = 0.04) but also demonstrated a smaller ΔHgb post-PRB (1.3 ± 1.0 versus 1.8 ± 0.8 versus 3.2 ± 1.6, P < 0.0001) compared with patients with higher pre-PRB Hgb, yet still received a transfusion. CONCLUSIONS: While patients with lower pre-PRB Hgb have more of the traditional risk factors for a complication after PRB, there was actually less clinically evident bleeding in these patients who were transfused. Although anemia itself has been considered to be a risk factor for a complication in the past, it more accurately represents only a predictor of receiving an erythrocyte transfusion. In the setting of the PRB, the decision for transfusion is influenced more by the severity of anemia at baseline as opposed to clinically evident bleeding.

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.

The variable course of women with X-linked Alport Syndrome.

X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss. Nearly all affected males have decreased kidney function resulting in end-stage renal disease (ESRD) as early as the second decade of life. It was long thought that affected females had a benign outcome; however, in recent decades, it has become quite clear that they too are at risk for developing nephrotic syndrome, decreased kidney function and ESRD. We report two young females presenting with microscopic hematuria and proteinuria diagnosed with XLAS on renal biopsy. Both developed nephrotic-range proteinuria and progressive renal insufficiency. Additionally, both developed extra-renal manifestations of XLAS. The ultrastructural and immunofluorescence features on kidney biopsy were instrumental in making the diagnosis of heterozygous XLAS as neither patient had a family history of AS.

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.

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.

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.