Shorter observation times and smaller gauge needles in outpatient kidney biopsies.

Controversy exists as to the optimal observational time (OT) after outpatient percutaneous kidney biopsy. Further, there is some uncertainty about the benefit of smaller (18-gauge) vs. larger (16-gauge) biopsy needles. At our institution, we have been lowering the OT after outpatient kidney biopsies. Initially in 2015, we were monitoring for 6 hours and gradually began to decrease the OT over time. From 2020, we have adopted an OT of less than 4 hours. During this time period (in 2018), we also began using a smaller gauge needle (18 gauge). We reviewed all outpatient kidney biopsies performed by the nephrology division at our institution since 2015. There were 137 biopsies reviewed. 63 had OT of 4 - 6 hours, and 74 had OT < 4 hours. There was a total of 4 significant complications (2.9%). Two complications, symptomatic retroperitoneal bleeds, were detected in less than 3 hours. The other 2 complications were seen at 9 hours (clot retention) and 72 hours (retroperitoneal bleed after anticoagulation restarted). 63% of the biopsies were done using 18-gauge needles with 1 complication in this group vs. 3 in the 16-gauge group. All cases had adequate tissue for interpretation based on the ability to make a kidney diagnosis. The number of glomeruli obtained in the 18-gauge group was 29 ± 13 glomeruli, and in the 16-gauge group was 25 ± 10, which did not differ between groups. In summary, in an outpatient population, all significant post-biopsy complications were evident either within the first 3 hours or after 9 hours, and this suggests the feasibility of using shorter than standard OT in outpatient kidney biopsies. Furthermore, an 18-gauge needle may lower the risk of complications and obtain adequate tissue.

Implication of acute tubular injury in minimal change nephrotic syndrome.

While acute tubular injury (ATI) is known to occur in a significant number of minimal change disease (MCD) nephrotic syndrome cases with acute kidney injury (AKI), the clinical significance is not certain, and AKI may also occur without ATI. This study aimed to evaluate whether the severity of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria correlated with the presence or severity of ATI in a series of adult patients with MCD. We also looked at whether time to remission of nephrotic syndrome (NS) with treatment correlated with the presence of ATI in those with and without AKI. We excluded patients with secondary MCD. Of 61 patients, 20 had AKI (33%). ATI was significantly more likely to occur in those with AKI than in those without AKI (60 vs. 24%). Overall, the severity of AKI did not clearly correspond with the severity of ATI. Remission rates at 4 weeks were lowest (25%) in those with both AKI and ATI, while they were highest (100%) in those with neither AKI nor ATI. Patients with AKI but no ATI and those with no AKI but having ATI were intermediate in remission rates and similar to each other (60 and 62%, respectively). The time to remission in the group of those without AKI was significantly longer in those with ATI than in those without (p = 0.0027), but the numerical difference in remission did not reach statistical significance in the smaller group of AKI patients. Patients with ATI were older and more often male than those without ATI. It appears that having ATI may predict a slower remission rate in MCD though the reason for this is unclear. The different demographics of those with ATI may also play a role.

Oxalate nephropathy: a review.

This review describes the clinical and pathological features of oxalate nephropathy (ON), defined as a syndrome of decreased renal function associated with deposition of calcium oxalate crystals in kidney tubules. We review the different causes of hyperoxaluria, including primary hyperoxaluria, enteric hyperoxaluria and ingestion-related hyperoxaluria. Recent case series of biopsy-proven ON are reviewed in detail, as well as the implications of these series. The possibility of antibiotic use predisposing to ON is discussed. Therapies for hyperoxaluria and ON are reviewed with an emphasis on newer treatments available and in development. Promising research avenues to explore in this area are discussed.

Adult primary nephrotic syndrome trends by race: a diminished frequency of focal segmental glomerulosclerosis in non-black patients.

PURPOSE: There have been conflicting data on the relative frequency of common forms of primary nephrotic syndrome (PNS). We undertook this study to look at the causes of PNS in the latest decade from our biopsy population, with a special attention to breakdown by race. METHODS: Retrospective chart review of all cases of adult PNS extracted from a database of 1388 cases for the last 10 years. We were careful to exclude patients with secondary disease and without the full nephrotic syndrome. RESULTS: There were 115 cases of PNS. Overall, MN was the most common lesion (40.0%), followed by minimal change disease (MCD) (34.0%), focal segmental glomerulosclerosis (FSGS) (13.0%), and IgA nephropathy (IgAN) (11.3%). Among whites, MN was the most common cause of NS (41.7%), followed by MCD (33.3%), IgAN (16.7%), and FSGS (6.3%). Among blacks, FSGS was the most common lesion (33.3%) followed closely by MN (29.6%), and MCD (26.0%). IgAN was present in 7.4%. Among multiracial patients (MR), MGN was the most common (50%) followed by MCD (45.5%) and FSGS (4.5%). In Asians, MCD (50.1%) and MGN (33.3%) were the most common, followed by FSGS and IgAN with 8.3% each. CONCLUSIONS: MN and MCD were the most common causes of PNS in our population, with FSGS much less common overall. This is especially the case among whites and MR. Among blacks, MN and FSGS were almost codominant causes. The apparent decreased prevalence of FSGS may be related to more effective exclusion of secondary and maladaptive causes.

Kidney oxalate crystal deposition in adult patients: A relatively common finding
.

AIMS: We aim to describe the clinical and histological findings in patients with the finding of any tubular oxalate deposits in kidney biopsy specimens. BACKGROUND: The prevalence, manifestation, and outcome of secondary oxalate nephropathy have not been extensively studied. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed the clinical and histological findings in all patients with the finding of any tubular oxalate deposits in kidney biopsy specimens between July 1, 2017, and December 31, 2018, at Northwell Health Pathology Department (Manhasset, NY, USA). RESULTS: The prevalence of oxalate deposition on a kidney biopsy was 4.07% (25/615), and in 88% of cases was a major finding. Prior to biopsy, oxalate was anticipated in only 1 case. The etiology of oxalosis was clarified retrospectively in 14 cases, most commonly due to GI surgery (n = 10) and increased oxalate intake (n = 4). In 11 cases, etiology remained unknown, although at least 3 cases were exposed to antibiotics associated with secondary oxalosis. There was no significant clinical/pathological or survival difference between known vs. unknown cause groups. The overall 3-month renal survival rate was 76.0 ± 8.5%. Multivariate Cox regression showed that creatinine at the time of biopsy (HR: 1.79, 95% CI: 0.71 - 4.51), background histological chronicity change (HR: 1.82, 95% CI: 0.70 - 4.72) and oxalate density (HR: 2.27, 95% CI: 0.49 - 10.55) are associated with end-stage kidney disease. CONCLUSION: Oxalate deposition is common but rarely anticipated biopsy finding. Nephrologists need to consider surgical history and other secondary causes of oxalosis as causes of acute kidney injury and chronic kidney disease.

Fibrillary Glomerulonephritis: An Update.

Fibrillary glomerulonephritis (FGN) is a rare proliferative form of glomerular disease characterized by randomly oriented fibrillar deposits with a mean diameter of 20 nm. By immunofluorescence (IF), the deposits stain for IgG, C3, and κ and λ light chains, suggesting that the fibrils may be composed of antigen-antibody immune complexes. A recent major advance in our understanding of the pathogenesis of FGN resulted from the discovery that a major component of the fibrils is DNA-J heat-shock protein family member B9 (DNAJB9), and immunohistochemical staining for DNAJB9 now makes it possible to diagnose FGN in the absence of ultrastructural evaluation. FGN has a poor prognosis, treatment options are currently limited, and transplant recurrence is not uncommon.

Prevalence of Proteinuria and Albuminuria in an Obese Population and Associated Risk Factors.

Obesity has been increasingly recognized as a risk factor for kidney disease and both proteinuria and microalbuminuria have been associated with obesity. The actual prevalence of microalbuminuria and proteinuria in obese patients in the United States (US) has not been clearly described in the literature. Furthermore, obesity is associated with risk factors of kidney disease, such as diabetes and hypertension (HTN), and the prevalence of proteinuria and albuminuria excluding these risk factors is uncertain. In this study, we collected urine albumin/creatinine and urine protein/creatinine ratios on obese patients undergoing bariatric surgery to determine the prevalence of albuminuria and proteinuria in obese patients with and without associated diabetes and HTN. The study included 218 obese patients undergoing bariatric surgery at a New York City hospital. The mean age was 42.1 ± 11.3 years. The mean body mass index (BMI) was 43.9 ± 8.1. Diabetes (DM) was present in 25%. HTN was present in 47%. The prevalence of proteinuria and albuminuria was 21% (95% CI: 15.8-27.1%) and 19.7% (95% CI: 14.2-26.2%) respectively. Among those without DM but who had HTN, 22.6% (95% CI: 12.9-35) had proteinuria and 17% (95% CI 8.4-30.9) had albuminuria. Of patients with neither DM nor HTN, 13.3% (95% CI: 7.3-21.6) and 11% (95% CI: 5-17%) had proteinuria and albuminuria, respectively. Diabetics had a significantly higher prevalence of proteinuria and albuminuria than the non-diabetic groups. The non-diabetic groups did not differ significantly from each other in terms of prevalence of proteinuria and albuminuria. The BMI for diabetics did not differ from non-diabetics. On multivariate analysis, only the presence of diabetes was associated with proteinuria and albuminuria. BMI, age, and HTN were not predictive. In conclusion, we found a relatively high prevalence of microalbuminuria and proteinuria in an urban, US, obese population undergoing bariatric surgery. When diabetics were excluded, there was a lower prevalence. Even patients who had neither diabetes nor HTN, still, however, had much greater amounts than seen in the general US population, likely reflecting an adverse effect of obesity itself on renal physiology.

Mycophenolate mofetil as a steroid-sparing agent in sarcoid-associated renal disease.

Steroids are the mainstay of treatment for renal sarcoidosis. Many patients with sarcoidosis are chronically dependent on steroids and there is limited data on the use of steroid-sparing agents. This is a case of a patient that has remained in remission using mycophenolate mofetil (MMF) as a steroid-sparing agent. The patient is a 56-year-old female with a history of sarcoidosis diagnosed by lymph node biopsy who developed 3 episodes of acute kidney injury (AKI) in the setting of exacerbations of her sarcoidosis, each responding to prednisone treatment. Due to possible lifelong need for prednisone, MMF was started as a steroid-sparing treatment. She tolerated the MMF well and has now been steroidfree for 22 months. There have been only a few case reports about the use of MMF as a steroid-sparing agent in sarcoid-associated renal disease, in which patients could be successfully weaned off steroids. This is the longest reported follow-up of a patient being off steroids while on MMF. It is also notable for the patient having a relapse on the MMF which responded to an increased dose. MMF should be studied further as a potential steroid-sparing agent in the treatment of sarcoid associated renal disease.

Characteristics, therapies, and factors influencing outcomes of hospitalized hypernatremic geriatric patients.

PURPOSE: Hypernatremia is a common electrolyte disorder associated with adverse outcomes such as increased length of stay and mortality due to a variety of factors. Our aim was to investigate known factors as well as other variables which we had identified in hospitalized hypernatremic geriatric patients and their relationship to patient outcomes. METHODS: A retrospective chart review of all adult hospitalized patients in a 4-month period with a serum sodium level >150 mmol/L was performed. Factors evaluated included use of a nephrology consultation, certain urine laboratory measures, fluids employed, rate of correction, and patient's level of care setting. Outcome measures included length of stay and mortality. RESULTS: The patient mortality rate was 52 %. Mean age was 79.6 years (n = 33), and mean initial sodium level was 152.6 mmol/L. Plasma and urine osmolality, and urine sodium concentration were checked in less than 25 % of patients. Fifteen of 18 patients in the ICU expired, whereas only 2 of 15 patients not in the ICU expired (p < 0.0004, OR 32.50, CI 95 % (4.68-225.54)). Of the 23 patients (70 %) who had their serum sodium level corrected, 11 were corrected in ≤3 days and 12 in >3 days, but this difference did not affect mortality rate (45 vs. 50 %, p = 0.99). The mortality rate was similar (60 %, p = 0.52) for those whose serum sodium level never corrected suggesting that correction did not influence outcomes. The fluids chosen for therapy of the hypernatremia were appropriate to the patients volume status. Five of 15 patients who received a nephrology consultation survived, while 11 of 18 patients without a nephrology consultation survived (p = 0.12). The mean length of stay was 25.0 ± 23.9 days and no different for those who expired versus those who survived (25.2 ± 21.2 vs. 24.8 ± 25.9 days, p = 0.96). CONCLUSIONS: Hypernatremia is associated with a poor prognosis, and outcomes are still disappointing despite appropriate rates of correction, intensive monitoring, and the involvement of a nephrologist. Strategies directed at avoidance of the development of hypernatremia and attention to concomitant disease may provide significant patient benefit.

Neurofibromatosis type 1-associated hypertension secondary to coarctation of the thoracic aorta.

Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is an autosomal dominant genetic disorder. NF-I vasculopathy has been used to describe various vascular malformations associated with NF-1. Secondary hypertension related to NF-1 vasculopathy has been reported because of renal artery stenosis, coarctation of the abdominal aorta and other vascular lesions; however, coarctation of the thoracic aorta has seldom been reported. We report the first case, to our knowledge, of isolated coarctation of thoracic aorta in a pregnant female with NF-1. Healthcare providers caring for patients with NF-1 should be aware of associated vascular complications.

Troponin I as a prognostic marker of cardiac events in asymptomatic hemodialysis patients using a sensitive troponin I assay.

Elevated troponin T is known to be a prognostic marker for long-term cardiac events and mortality in asymptomatic end-stage renal disease patients. There are conflicting data in this regard with respect to troponin I (TnI). We recently showed a high incidence of elevated TnI levels in asymptomatic hemodialysis (HD) patients using a new generation sensitive TnI assay. The aim of this pilot study was to explore the prognostic value of TnI, as measured with this new assay, as a marker for outcomes in HD patients over a 2-year follow-up period. Fifty-one asymptomatic HD patients were enrolled, and pre-dialysis TnI levels were checked once monthly over 3 consecutive months. Patients were considered to be in the TnI positive group if TnI level on any of the three draws was ≥0.035 ng/ml. All patients were followed for a period of 2 years. The primary end points were acute coronary syndrome, coronary revascularization, sudden death, or cardiac arrest. The secondary end point was all-cause mortality. Elevated TnI levels were found in 51% (26/51) of patients in our cohort. One TnI positive patient was subsequently lost to follow up. There were 6 cardiac events over 2 years, all of which were in the troponin positive group (6/25 or 24%). The presence of a positive TnI at baseline was significantly associated with future cardiac events (p=0.022). A prior history of coronary artery disease (CAD) was also significantly related to future cardiac events (p=0.010). No patient with negative TnI at baseline developed a cardiac event, while 45.5% of those with both a positive TnI and a history of CAD had an event. Fourteen deaths occurred over 2 years, 8 in TnI positive and 6 in the negative group. All-cause mortality was not associated with elevated TnI levels at baseline. We found a significant association between positive TnI and subsequent cardiac events in asymptomatic HD patients followed for 2 years. TnI levels, as measured with a sensitive assay, may be useful in assessing cardiac risk in asymptomatic HD patients. This needs further confirmation in a larger cohort.

Troponin I levels in asymptomatic patients on haemodialysis using a high-sensitivity assay.

BACKGROUND: Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. METHODS: We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. RESULTS: At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (≥0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. CONCLUSION: Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level.

Impact of heart failure on the incidence of contrast-induced nephropathy in patients with chronic kidney disease.

We randomized patients with chronic kidney disease (serum creatinine ≥ 1.5 mg/dl or glomerular filtration rate (GFR) <60 ml/min/1.73 m²) in a double-blind fashion to receive saline or sodium bicarbonate prior to and after cardiac or vascular angiography. The primary endpoint was contrast-induced nephropathy (CIN), defined as an increase in serum creatinine by 25% or by 0.5 mg/dl from baseline. Patients with congestive heart failure (CHF), cardiac ejection fraction (EF) <30%, or GFR < 20 ml/min/1.73 m² were excluded. The study was discontinued (after 142 patients were randomized) due to a low incidence of CIN (1.5%). We retrospectively identified all cases of CIN (n = 30) at our institution during the same time period to see if these patients differed from our trial sample. There was no difference in serum creatinine (1.7 ± 0.4 vs. 1.7 ± 0.6 mg/dL), GFR (42.7 ± 9.7 vs. 45.3 ± 3.2 ml/min), incidence of diabetes (51.8% vs. 63.3%), contrast volume (121.7 ± 63.8 vs. 122.7 ± 68.3 ml), ACE inhibitor or angiotensin receptor blocker use (54.0% vs 63.3%), and periprocedure diuretic use (33.1% vs 26.7%). On multivariate analysis, only a cardiac ejection fraction (EF) of less than 40% was significantly associated with CIN (odds ratio, 4.52; 95% confidence interval, 1.30-15.71; P = 0.02). In all, 22/30 patients (73.3%) who developed CIN had at least one or more characteristics that would have excluded their enrollment in our randomized trial including evidence of congestive heart failure (17/30 patients), EF less than 30% (9 patients), age greater than 85 years (2 patients), or advanced renal failure with a baseline GFR of less than 20 cc/min (1 patient). In summary, patients with CKD without evidence of CHF who receive adequate hydration appear to have a very low risk of CIN associated with angiography. A low EF (less than 40%) appeared to be the most significant risk factor for CIN in our population.

The effect of withdrawal of ACE inhibitors or angiotensin receptor blockers prior to coronary angiography on the incidence of contrast-induced nephropathy.

BACKGROUND: The effect of continuing or discontinuing chronic angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to coronary angiography on the incidence of contrast-induced nephropathy (CIN) is not clear. We undertook a randomized trial to evaluate the effect of withdrawing ACEIs or ARBs 24 h prior to coronary angiography on the incidence of CIN associated with coronary angiography. METHODS: A total of 220 patients with chronic kidney disease (CKD) stages 3-4 (glomerular filtration rate 15-60 ml/min/1.73 m2) on ACEI or ARB therapy were randomized before angiography to either ACEI/ARB continuation group or discontinuation group. A third group of patients with CKD stages 3-4 but not on angiotensin blockade therapy were also followed. The primary outcome measure was the incidence of CIN defined by a rise in serum creatinine by 25% or 0.5 mg/dl (44 micromol/l) from baseline. RESULTS: There was no statistically significant difference in the incidence of CIN between the three groups (P=0.66). The incidences were 6.2%, 3.7%, and 6.3% for the continuation, discontinuation, and angiotensin blockade naïve group, respectively. There was also no significant difference found between the groups in mean serum creatinine and glomerular filtration rate values at baseline and post contrast administration. CONCLUSION: Withholding ACEIs and ARBs 24 h before coronary angiography does not appear to influence the incidence of CIN in stable patients with CKD stages 3-4.

Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features.

BACKGROUND: Controversy surrounds the relatedness of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulonephritis (IT). METHODS: To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of Congo red-negative randomly oriented fibrils of < 30 nm (mean, 20.1 +/- 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of > or = 30 nm (mean, 38.2 +/- 5.7 nm). RESULTS: FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were immunoglobulin G (IgG) dominant and polyclonal in 96%. IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two IgG1 and two IgG4) and oligotypic deposits in 15 (all combined IgG1 and IgG4). In IT, deposits were IgG dominant in 83% and monoclonal in 67% (three IgG1 kappa and one IgG1 lambda). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range): creatinine 3.1 mg/dL (0.5 to 14), proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59% hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative glomerulonephritis (DPGN) (nine cases), membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13), membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher creatinine and greater proteinuria compared to MES and MGN. Median time to end-stage renal disease (ESRD) was 24.4 months for FGN and mean time to ESRD varied by histologic subtype: DS 7 months, DPGN 20 months, MPGN 44 months, compared to MES 80 months and MGN 87 months. There was no statistically significant effect of immunosuppressive therapy (given to 36% of FGN patients). By Cox regression (hazard ratio, confidence interval, P value), independent predictors of progression to ESRD were creatinine at biopsy [2.05 (1.55 to 2.72) P < 0.001] and severity of interstitial fibrosis [2.01 (1.05 to 3.85) P = 0.034]. Although IT had similar presentation, histologic patterns, and outcome compared to FGN, it had a greater association with monoclonal gammopathy (P = 0.014), underlying lymphoproliferative disease (P = 0.020), and hypocomplementemia (P = 0.032). CONCLUSION: FGN is an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant renal insufficiency and have a poor outcome despite immunosuppressive therapy, and outcome correlates with histologic subtype. By contrast, IT often contains monoclonal IgG deposits and has a significant association with underlying dysproteinemia and hypocomplementemia. Differentiation of FGN from the much more rare entity IT appears justified on immunopathologic, ultrastructural, and clinical grounds.

Fludarabine treatment of cryoglobulinemic glomerulonephritis.

Three patients (one hepatitis C positive) presented with renal insufficiency and nephrotic-range proteinuria resulting from mixed cryoglobulinemia and glomerulonephritis. All three patients received two to four cycles of intravenous fludarabine (each cycle consisted of 25 to 50 mg/d for 4 to 5 days). All patients responded to therapy with a decrease in proteinuria, increase in serum albumin, and decrease in serum creatinine. This response was evident by 2 months and persisted for 2 to 5 years. In two patients, this response was accompanied by disappearance of cryoglobulins, at least transiently. One patient developed tuberculosis with neutropenia. Transient blindness and neutropenia were seen in another patient. These results suggest that fludarabine may be a useful treatment in cryoglobulinemia with glomerulonephritis, although its use may be accompanied by side effects.