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.

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.

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.

Massive intravascular hemolysis with mechanical rheolytic thrombectomy of a hemodialysis arteriovenous fistula.

A 57-year-old man with chronic kidney disease stage 5 presented for ambulatory evaluation of his arteriovenous fistula. He underwent rheolytic thrombectomy with tissue plasminogen activator infusion, angioplasty, and brachial artery stenting under local sedation. His immediate postoperative course was complicated by hypotension, cardiac dysrhythmias and hyperkalemia requiring emergent hemodialysis, due to severe intravascular hemolysis. This case illustrates that mechanical thrombectomy can cause clinically significant intravascular hemolysis, thus careful postoperative monitoring is recommended.

Safety and efficacy of local periadventitial delivery of sirolimus for improving hemodialysis graft patency: first human experience with a sirolimus-eluting collagen membrane (Coll-R).

BACKGROUND: Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. METHODS: A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. RESULTS: There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. CONCLUSIONS: Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.

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.

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.

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.

Novel Approaches to Arteriovenous Access Creation, Maturation, Suitability, and Durability for Dialysis.

Since the arteriovenous fistula (AVF) was first conceived over 50 years ago, the goal to create a vascular conduit with predictable and reproducible maturation and durability continues to elude caregivers. Recently, however, advances in the understanding of vascular biology and new technologies now provides us with some optimism; we are moving toward a viable solution. A quickly maturing, sustainable, and durable arteriovenous access may soon be attainable. This review will discuss these advances. There are novel approaches to AVF creation and devices to enhance maturation, advances in arteriovenous graft material(s), and devices to safely prolong the use of tunneled dialysis catheters. Although hemodialysis (HD) access remains a complex problem, these innovations may lead the way to optimizing the care and the quality of life of those patients who have no choice but to proceed with HD.

Observations regarding the use of the aquaretic agent conivaptan for treatment of hyponatremia.

The treatment of hyponatremia, especially euvolemic and hypervolemic hyponatremia, has changed with the development of drugs which function as vasopressin receptor antagonists. These agents increase solute-free water excretion by the kidney resulting in an aquaresis. Conivaptan, a vasopressin receptor antagonist, has recently been approved by the FDA in the United States for use in the therapy of both euvolemic and hypervolemic hyponatremia. This report summarizes one center's experience with ten patients treated with this new drug. The patients had euvolemic hyponatremia with serum sodium levels less than 128 mEq/l. The same protocol was used in all patients with the conivaptan being given as a 20-mg intravenous loading dose followed by a 20-mg continuous 24-h infusion. Review of the data revealed that six of the ten patients had an excellent response to the therapy, with serum sodium increasing by a mean of 8.5+/-0.8 mEq/l (increases ranged from 7 to 12 mEq/l over 24 h). No significant changes in serum potassium levels or mean arterial pressures were noted. Two of the ten patients experienced a decrease in urine osmolality without a significant increase in serum sodium. Two other patients had only slight decreases in urine osmolality, and no significant increase in serum sodium levels. The data reveal that conivaptan is useful in the management of significant hyponatremia. There were no significant untoward effects, with the exception of one patient whose blood pressure decreased during the conivaptan infusion and who responded to cessation of the infusion and saline replacement therapy. This new class of drugs holds great promise for the treatment of dilutional hyponatremic disorders.

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.

Use of lung ultrasonography to determine the accuracy of clinically estimated dry weight in chronic hemodialysis patients.

PURPOSE: The use of lung ultrasound (LUS) to identify extravascular lung water has received increasing acceptance. Sonographic B-lines, discrete vertical lines that originate from the pleura, represent pulmonary edema and are correlated with the accumulation of fluid. The goal of this study was to evaluate the utility of LUS to determine the accuracy of prescribed dry weight (DW) in chronic hemodialysis (HD) patients and to ascertain the adequacy of fluid removal. METHODS: LUS was scheduled to be performed pre- and post-HD in 20 patients. The HD prescription and DW challenge were done independent of the results of the LUS. The presence of B-lines was tabulated and compared to the intradialytic ultrafiltration parameters. RESULTS: Of the 20 patients, 3 did not exhibit B-lines at the first dialysis session. In regard to the other 17 patients, B-lines disappeared in 7 patients at the end of the HD session (mean B-lines 4.2-0). One patient was 0.3 kg away from the prescribed dry weight, but the 6 patients were a mean of 1.7 kg below DW. Of the remaining 10 patients, eight decreased but did not eliminate the B-lines (mean B-lines 15.5-3.8) and were a mean of 3.8 kg below DW post-HD. Two patients who exhibited more cardiac insufficiency than initially recognized could not reach DW or eliminate the B-lines. Eight patients who had residual B-lines at the end of the first HD session had their DW re-estimated and had a second session. Two were able to eliminate the B-lines (mean 2.5-0) and reached a mean of 1.2 kg below DW. Six did not eliminate the B-lines (mean 11.5-4.2) but were able to reach a mean of 0.6 kg below DW. Correlation analysis showed a statistically significant correlation (P < 0.05) between the intradialytic percent change in B-lines and the percent change in total body weight (r = 0.40) and ultrafiltration rate (r = 0.33). Seven of 10 patients with clear chest X-rays pre-HD exhibited B-lines. CONCLUSIONS: This study supports the hypothesis that reduction in B-lines during HD can provide accurate information regarding changes in pulmonary fluid content. Further, LUS is a valuable diagnostic tool for recognizing both the adequacy of fluid removal and the occurrence of error in the estimation of dry weight by usual clinical parameters.

Oral vitamin C supplementation reduces erythropoietin requirement in hemodialysis patients with functional iron deficiency.

PURPOSE: Functional iron deficiency (FID) is a major cause of persistent anemia in dialysis patients and also contributes to a suboptimal response to erythropoietin (Epo) administration. Vitamin C acts as an enzyme cofactor and enhances mobilization of the ferrous form of iron to transferrin thus increasing its bioavailability. High-dose intravenous vitamin C has been shown to decrease the Epo requirement and improve hemoglobin levels in previous studies. This study assessed the effect of low-dose oral vitamin C on possible reduction in Epo dose requirements in stable hemodialysis patients with FID. METHODS: This prospective study included 22 stable hemodialysis patients with FID defined as transferrin saturation (T sat) <30 % and ferritin levels of >100 mcg/L with Epo requirement of ≥4000 U/HD session. Patients received oral vitamin C 250 mg daily for 3 months. Hemoglobin, iron and T sat levels were recorded monthly. No one received iron supplementation during the study period. RESULTS: There was a significant reduction in median Epo dose requirement in the 15 patients who completed the study, from 203.1 U/kg/week (95 % CI 188.4-270.6) to 172.8 U/kg/week (95 % CI 160.2-214.8), (P = 0.01). In the seven responders, there was 33 % reduction in Epo dose from their baseline. Despite adjustment of Epo dose, the mean hemoglobin level was significantly increased from 10.1 ± 0.6 to 10.7 ± 0.6 mg/dL (P = 0.03). No adverse effects of oral vitamin C were observed. CONCLUSION: Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID. Limitations of this study include a small sample size and the lack of measurements of vitamin C and oxalate levels. Despite concerns regarding oral vitamin C absorption in dialysis patients, this study indicates vitamin C was well tolerated by all participants without reported adverse effect.

Epidemiology and Challenges to the Management of Advanced CKD.

Advanced CKD is a period of CKD that differs greatly from earlier stages of CKD in terms of treatment goals. Treatment during this period presents particular challenges as further loss of kidney function heralds the need for renal replacement therapy. Successful management during this period increases the likelihood of improved transitions to ESRD. However, there are substantial barriers to optimal advanced CKD care. In this review, we will discuss advanced CKD definitions and epidemiology and outcomes.

Pregnancy in peritoneal dialysis: a case report and review of adequacy and outcomes.

A case of pregnancy in a 27-year-old woman on peritoneal dialysis is presented. The case report is a detailed description of her course including changes in her peritoneal dialysis regimen and the use of continuous cycling to maximize dialysis adequacy while addressing the patient's recurrent abdominal pain and fullness. Also described is the management of complications including hypertension, gestational diabetes, and premature rupture of membranes. The discussion reviews the diagnosis of pregnancy, factors that may relate to outcome, and a detailed comparison of pregnancy outcomes in patients on dialysis to the general population.

A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin.

The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive function. Important cellular responses including cell proliferation, inflammation, and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic-pituitary-adrenal axis are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance.

Refractory hypotension and edema caused by right atrial compression in a woman with polycystic kidney disease.

We present the case of a 60-year-old woman with a history of autosomal dominant polycystic kidney disease and long-standing hypertension who developed persistent hypotension. While in the hospital for the treatment of bacteriemia, the patient had low systolic blood pressures (90 to 100 mm Hg), which was thought to be the consequence of infection. After the infection was adequately controlled and the blood pressure did not improve, an echocardiogram was done to further elucidate her hypotension. It was nondiagnostic and revealed an ejection fraction of 70% with left ventricular hypertrophy. Shortly after discharge, she developed significant lower extremity edema and her blood pressure remained low. Due to the low blood pressure it was not possible to mobilize the fluid with her dialysis treatments. A repeat transthoracic echocardiogram at that time revealed that the right atrium was partially compressed throughout the cardiac cycle by polycystic hepatic tissue. This tissue invaginated up through the right hemidiaphragm. A partial liver resection was considered for the patient. Instead, right nephrectomy was performed and the blood pressure improved.

Failure of intravenous fluid therapies to decrease serum sodium levels in elderly hospitalized patients.

Elderly patients may have a tendency to develop hyponatremia due to sensitivity to stimuli that release ADH as well as an impaired ability to excrete a water load. We evaluated changes in serum sodium in elderly hospitalized patients who received various forms of intravenous fluid therapies. All patients were required to have a baseline serum sodium of 136-145 meq/L. Fourteen patients were enrolled in the study. The mean age was 82.9 +/- 6.8 years (mean +/- SEM). Thirty-six % were nursing home residents. Seventy-nine % were females. Seventy-two % received half normal saline and the remainder received normal saline as intravenous fluid therapy. The patients received a mean of 1098 +/- 145 mL of intravenous fluid per day, in addition to oral fluids. Mean follow up period was 5.9 days (3-10 days). Mean baseline serum sodium was 140.2 +/- 0.7 meq/L andmean follow up serum sodium was 141.4 +/- 0.9 meq/L. The m ean baseline BUN was 25 +/- 3.6 mg/dL and mean follow u BUN was 19.6 +/- 3.4 mg/dL. The mean baseline serum creatinine was 0.9 +/- 0.1 mg/dL and mean follow up creatinine was 0.9 +/- 0.1 mg/dL. The postintravenous fluid therapy serum sodium in the group receiving half normal saline was 141.7 +/- 0.7 meq/L and 140.8 +/- 3 meq/L in the normal saline group. No significant difference was observed between the pre and post fluid therapy for any of these paramenters (p > 0.05). Mean baseline plasma renin activity was 1.6 +/- 0.7 ng/ml/hour and fifty-seven % had PRA of less than 1 ng/ml/hour. Mean plasma aldosterone was 8.5 +/- 1.8 ng/mL and forty-two % were less than 5.5 ng/mL. Plasma ADH and ANP was 5.7 +/- 3.4 pg/mL and 83.6 +/- 26.9 pg/mL, respectively. Mean serum and urine osmolalities were 290 +/- 3.1 mOsm/kg and 471 +/- 57.7 mOsm/kg, respectively. No patient developed hyponatremia and 7 of the 14 patients experienced an increase in serum sodium during the follow up period. We conclude that many elderly patients hospitalized for acute medical illnesses either maintain a stable serum sodium or experience an increase in serum sodium. This occurs because total fluids administered to these patients are generally insufficient.