Chronic kidney disease recognition amongst physicians and advanced practice providers.

OBJECTIVE: Chronic kidney disease is a worldwide public health issue, with increasing prevalence resulting in high morbidity and mortality. As a result, recognizing and treating it early can lead to improved outcomes. We hypothesized that some providers might be more comfortable making this diagnosis than others. METHODS: Retrospective study of 380 patients with chronic kidney disease seen between 2012 and 2016 in an outpatient setting. RESULTS: Three hundred and sixteen patients were treated by physicians and sixty-four by advanced practice providers. Chronic kidney disease was identified by the primary care providers in 318 patients (83.6%). Patients recognized with chronic kidney disease were older, 76 ± 8.8 vs 72 ± 7.45 years, p = 0.001; had lower GFR, 37 [29, 46] vs 57 [37, 76] ml/min/1.73 m2, p < 0.0001 and were more likely to be seen by a physician compared to an advanced practice provider: 272/316 (86%) vs 46/64 (71.8%), p = 0.008. In multivariate analyses, care by a physician, OR = 2.27 (1.13-4.58), p = 0.02 was associated with increased recognition of chronic kidney disease. On the other hand, higher GFR was associated with decreased diagnosis of chronic kidney disease, OR = 0.95 (0.93-0.96), p < 0.0001. CONCLUSION: The odds of chronic kidney disease recognition were higher amongst physicians in comparison to non-physician providers.

Long term follow up of biomarkers of podocyte damage and renal function in patients with and without preeclampsia.

INTRODUCTION: preeclampsia can be associated with future renal disease. OBJECTIVES: To measure changes in renal function overtime in patients with preeclampsia. METHODS: urine and serum samples from eleven patients with preeclampsia and eight patients with a normal pregnancy were obtained during pregnancy, postpartum, and 3 years after delivery. Urine podocalyxin, protein, and serum creatinine were measured. RESULTS: after 3 years, there were no significant differences in urinary podocalyxin in patients with or without preeclampsia: 4.34 ng/mg [2.69, 8.99] vs. 7.66 ng/mg [2.35, 13], p = 0.77. The same applied to urinary protein excretion: 81.5 mg/g [60.6, 105.5] vs. 43.2 mg/g [20.9, 139.3] p = 0.23. Serum creatinine was 0.86 mg/dL [0.7, 0.9] vs. 0.8 mg/dL [0.68, 1] p = 0.74 in those with and without preeclampsia. In normal patients, urinary podocalyxin decreased from 54.4 ng/mg [34.2, 76.9] during pregnancy to 7.66 ng/mg [2.35, 13] three years after pregnancy, p = 0.01. Proteinuria decreased from 123.5 mg/g [65.9, 194.8] to 43.2 mg/g [20.9, 139.3], p = 0.12. In preeclampsia patients, urinary podocalyxin decreased from 97.5 ng/mg [64.9, 318.4] during pregnancy to 37.1 ng/mg within one week post-partum [21.3, 100.4] p = 0.05 and 4.34 ng/mg [2.69, 8.99] three years after, p = 0.003. Proteinuria was 757.2 mg/g [268.4, 5031.7] during pregnancy vs. 757.2 mg/g [288.2, 2917] postpartum, p = 0.09 vs. 81.5 mg/g [60.6, 105.5] three years later, p = 0.01. Two patients still had proteinuria after 3 years. CONCLUSIONS: in preeclampsia patients, postpartum urinary podocalyxin decreased before proteinuria. After three years, serum creatinine, urinary podocalyxin, and protein tended to normalize, although some patients still had proteinuria.

Systolic blood pressure values might further risk-stratify the adverse outcomes of LVH in older patients with chronic kidney disease.

BACKGROUND: LVH is highly prevalent in patients with CKD and is independently associated with subsequent cardiovascular events. We hypothesized that adding systolic blood pressure values to LVH might differentiate different subgroups of patients at higher risk of cardiovascular events (CVE) and other adverse outcomes. METHODS: Retrospective cohort study of 243 patients older than 60 years with stages 1-5 pre-dialysis CKD. LVH was assessed by electrocardiogram or echocardiogram. RESULTS: Cardiovascular events occurred in 7 patients (10.3%) among those with SBP <130 and no LVH, 8 patients (10.5%) among those with SBP ≥130 and no LVH, 7 patients (21.2%) among those with SBP <130 and LVH and 25 patients (37.9%) among those with SBP ≥ 130 and LVH. On multivariate analyses, comparing to SBP < 130 and no LVH, the HR for CVE in those with SBP ≥ 130 and LVH was 4 (1.75, 10.3), p = 0.0007; 2.13 (0.71, 6.32) p = 0.16 in those with SBP <130 and LVH and 1.20 (0.42, 3.51) p = 0.72 in those with SBP ≥130 and no LVH. No significant differences were noted in changes in renal function and mortality rates among the groups. CONCLUSION: The combination of higher systolic blood pressure and LVH might identify older patients with CKD at higher risk of cardiovascular outcomes.

Clinical outcomes with a systolic blood pressure lower than 120 mmHg in older patients with high disease burden.

BACKGROUND: The target blood pressure in older patients is controversial. Recent studies provided clinical evidence supporting a target systolic blood pressure <120 mmHg in patients >50 years at high risk of cardiovascular events. METHODS: Retrospective study of 380 consecutive patients ≥60 years with stages 1-5 pre-dialysis chronic kidney disease seen between January 2013 and November 2015. The outcomes of a systolic blood pressure <120 mmHg in older patients with chronic kidney disease and multiple comorbidities were analyzed. RESULTS: Sixty-eight patients had a systolic blood pressure <120 mmHg, 312 patients had a systolic blood pressure ≥120 mmHg. Forty-three patients died during the follow up (11.3%). Patients with a systolic blood pressure <120 mmHg had a higher risk of death: 21 (30.9%) vs 22 (7%). Primary cause of death: Cardiovascular: 11 (25.6%), infectious 9 (20.9%), cancer 5 (11.6%), renal failure 6 (13.9%), COPD/pulmonary fibrosis 2 (4.6%), end stage liver disease 3 (6.9%), traumatic brain injury 1 (2.3%), gastrointestinal hemorrhage 4 (9.3%), complications of diabetes 1 (2.3%), unknown 1 (2.3%). After adjusting for confounding factors, a systolic blood pressure <120 mmHg remained associated with increased mortality. There was a trend to more cardiovascular outcomes in those with a lower blood pressure. CONCLUSIONS: A systolic blood pressure below 120 mmHg in older patients with high disease burden was associated with adverse outcomes. Individualization of blood pressure therapy to each specific patient is warranted.

Intravenous lipid emulsion and high-dose insulin as adjunctive therapy for propranolol toxicity in a pediatric patient.

PURPOSE: The concurrent use of intravenous lipid emulsion (ILE) and high-dose insulin (HDI) for the management and treatment of propranolol toxicity in a pediatric patient is described. SUMMARY: A seven-month-old infant (weight, 6.1 kg) was admitted to a hospital emergency department with lethargy and bradycardia after an unintentional overdose of propranolol suspension, which had been prescribed several days previously for treatment of a scalp hemangioma. Notable physical examination and laboratory findings were as follows: blood pressure, 121/84 mm Hg (normal range, 90 ± 30/60 ± 10 mm Hg); heart rate, 62 beats/min (normal range, 100-150 beats/min); respiratory rate, 24 breaths/min (normal range, 25-35 breaths/min); oxygen saturation, 100% on room air; and rectal temperature, 35.7 °C (normal range, 36.6-38.0 °C). The patient was lethargic. Treatment included i.v. fluid boluses of 0.9% sodium chloride injection and i.v. boluses and continuous infusions of HDI, dextrose, and ILE. After the completion of these treatments, hemodynamic stability was regained. The case is believed to be the first reported case in which a pediatric patient less than one year of age regained hemodynamic stability after administration of ILE and HDI rescue therapy. Monitoring blood glucose frequently with HDI is essential to avoid hypoglycemia. The rationale for using ILE and HDI for reversal of drug toxicities is discussed. CONCLUSION: A symptomatic pediatric patient with acute propranolol toxicity exhibited clinical improvement with the administration of ILE in conjunction with HDI.

A Case of Hypophosphatemia with Increased Urinary Excretion of Phosphorus Associated with Ibrutinib.

Ibrutinib, an irreversible oral inhibitor of Bruton's tyrosine kinase, has been used in the treatment of patients with multiple hematologic malignancies. A 59-year-old male with chronic lymphocytic leukemia was treated with 420 mg/day of ibrutinib. No evidence of bruising or diarrhea was noted. The treatment was complicated by a transient increase in creatinine (from a baseline of 1.2 to 1.5 mg/dl) and potassium (reaching a peak of 6.5 mEq/l). Uric acid and calcium levels were normal. The patient developed hypophosphatemia (prior to initiation of therapy the serum phosphorus was 2.9 mg/dl). No metabolic acidosis was noted. Urinalysis showed no glucosuria or proteinuria. Urinary fraction of excretion of phosphate was found to be 345% (normal <5%). Because of these changes, ibrutinib was held, and the patient was given kayexalate. Serum potassium normalized. Serum phosphorus was checked a couple of weeks later and also normalized. A lower dose of ibrutinib (140 mg/day) was restarted. Upon follow-up, the phosphorus level has been between 2.9 and 3.2 mg/dl. No further evidence of hyperkalemia has been noted. Renal function has remained at baseline. To the best of our knowledge, this is the first case report describing the mechanism of hypophosphatemia in a patient treated with ibrutinib.

Avoidance of polypharmacy and excessive blood pressure control is associated with improved renal function in older patients.

BACKGROUND: Elderly patients are particularly susceptible to polypharmacy. The present study evaluated the renal effects of optimizing potentially nephrotoxic medications in an older population. METHODS: Retrospective study of patients' ≥ 60 years treated between January of 2013 and February of 2015 in a Nephrology Clinic. The renal effect of avoiding polypharmacy was studied. RESULTS: Sixty-one patients were studied. Median age was 81 years (range 60-94). Twenty-five patients (41%) were male. NSAIDs alone were stopped in seven patients (11.4%), a dose reduction in antihypertensives was done in 11 patients (18%), one or more antihypertensives were discontinued in 20 patients (32.7%) and discontinuation and dose reduction of multiple medications was carried out in 23 patients (37.7%). The number of antihypertensives was reduced from a median of 3 (range of 0-8) at baseline to a median of 2 (range 0-7), p < 0.001 after intervention. After intervention, the glomerular filtration rate (GFR) improved significantly, from a baseline of 32 ± 15.5 cc/min/1.73 m(2) to 39.5 ± 17 cc/min/1.73 m(2) at t1 (p < 0.001) and 44.5 ± 18.7 cc/min/1.73 m(2) at t2 (p < 0.001 vs. baseline). In a multivariate model, after adjusting for ACEIs/ARBs discontinuation/dose reduction, NSAIDs use and change in DBP, an increase in SBP at time 1 remained significantly associated with increments in GFR on follow-up (estimate = 0.20, p = 0.01). CONCLUSIONS: Avoidance of polypharmacy was associated with an improvement in renal function.

Urinary podocalyxin as a marker of preeclampsia in a Hispanic population.

BACKGROUND: Preeclampsia is associated with significant materno-fetal morbidity and mortality. Podocyturia due to podocyte damage seems to be associated with the disease. The objective of this study was to evaluate the usefulness of urinary podocalyxin as a marker of preeclampsia in a Hispanic population. METHODS: 63 patients were studied. 25 patients had preeclampsia/eclampsia (PE-E). 38 patients had normal pregnancies and served as control group. 24 hour proteinuria, urine protein/creatinine (UPC), urinary podocalyxin and perinatal outcomes were measured. A Podocalyxin ELISA test was used to detect podocyturia. RESULTS: Mean age (years), mean±SD was 30.5±5.4 in normal patients vs 30.6±5.8 in PE-E, p=0.98. Median gestational age (weeks) was, 38 (range 21-42) for normal pregnancies and 36 (range 24-40) for patients with PE-E, <0.001. Urine podocalyxin/creatinine on admission (ng/mg), median [IQR] in normal patients was 55.9 [29.4, 74.9] vs 109.7 [63.8, 234.1] in PE-E, p=0.001. After adjusting for admission proteinuria, urinary podocalyxin remained independently associated with preeclampsia: OR=1.0040 (95% CI 1.0003-1.0078), p=0.03. There was low to moderate correlation between UPC and urinary podocalyxin, Spearman's =0.31, p=0.01. In PE-E, post-partum urine podocalyxin was lower, median [IQR]: 69.7 [32.7, 184.8] p=0.19 vs admission. There was a trend towards more podocyturia and proteinuria in patients with eclampsia, comparing to those with preeclampsia. There was no association observed between podocyturia and neonatal mortality, IUGR or Apgar scores. CONCLUSIONS: Significantly higher levels of urinary podocalyxin are seen in preeclampsia/eclampsia. They tend to normalize after delivery.

Seronegative anti-GBM Disease with Coexistent ANCA Positivity.

Anti-glomerular basement membrane disease has been reported to coexist with anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis. Seronegative anti-GBM disease has been previously described and mostly blamed for the relative insensitivity of earlier serologic assays. A 58-year-old male was transferred to our facility for acute kidney injury. Prior to his hospital admission, the patient had a 2 week history of progressive fatigue, fevers, anorexia, vomiting, decreased urine output, sinus congestion, and non-productive cough. His creatinine reached 13 mg/dL. P-ANCA was positive, anti GBM antibody was negative twice, and urinalysis showed hematuria. Chest x-ray demonstrated diffuse opacities, concerning for pulmonary hemorrhage. Renal biopsy showed a severe necrotizing and crescentic glomerulonephritis with circumferential crescents. There was bright linear glomerular basement membrane staining with IgG consistent with anti-GBM disease. Given these findings, the patient was started on oral cyclophosphamide (160 mg daily), in addition to pulse dose methylprednisolone. He was also initiated on therapeutic plasma exchange. Due to worsening renal function, hemodialysis was started. The patient was discharged from the hospital and completed a course of treatment with cyclophosphamide and prednisone but remains oligo-anuric and hemodialysis dependent at 150 days since presentation. This case highlights the importance of tissue diagnosis in situations similar to this.

Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors.

BACKGROUND: The acceptance criteria used for living kidney donors are largely theoretical, as they are not clearly linked to outcomes. The goal of this study was to use implantation biopsies as a surrogate outcome marker to evaluate our living kidney donor selection criteria. METHODS: One thousand six hundred sequential living kidney donor biopsies were performed between 2001 and 2011. Implantation biopsies were assessed by dedicated renal pathologists according to the Banff criteria. Biopsies with any chronic score of 2 or higher were deemed to have moderate to severe changes (MSC). RESULTS: MSC was present in 4% (n=65) of implantation biopsies and occurred across a wide range of age and other demographics. By multivariate analysis, donor age (odds ratio [95% confidence interval], 1.060 [1.035-1.086]; P<0.0001) and donor systolic blood pressure (SBP) (odds ratio [95% confidence interval], 1.022 [1.006-1.037]; P=0.0060) were associated with MSC. Donor gender, body mass index, diastolic blood pressure, glomerular filtration rate, and urinary microalbuminuria were not. MSC was further increased in donors older than 60 years with SBP>140 (30% [7 of 23]) and donors older than 60 years with SBP>140 and glomerular filtration rate above the 25th percentile (42.8% [3 of 7]). In donors younger than 60 years, combining factors did not show an increased prevalence of MSC. At follow-up, renal function was similar in donors with and without MSC. CONCLUSIONS: MSC occurred sporadically in donors with varied characteristics. Although we did not detect patterns to support specific changes in our acceptance criteria, certain subgroups of donors might benefit from close follow-up.

Urine but not serum soluble urokinase receptor (suPAR) may identify cases of recurrent FSGS in kidney transplant candidates.

BACKGROUND: Recently, serum soluble urokinase receptor (suPAR) has been proposed as a cause of two thirds of cases of focal segmental glomerulosclerosis (FSGS). It was noted to be uniquely elevated in cases of primary FSGS, with higher levels noted in cases that recurred after transplantation. It is also suggested as a possible target and marker of therapy. METHODS: We studied serum and urine suPAR from pretransplantation banked samples from 86 well-characterized kidney transplant recipients and 10 healthy controls to determine its prognostic utility. Causes of native kidney disease were primary FSGS, diabetic nephropathy, membranous nephropathy, immunoglobulin A nephropathy, and autosomal dominant polycystic kidney disease. suPAR was measured using a commercially available enzyme-linked immunosorbent assay kit. Urinary suPAR was indexed to creatinine. RESULTS: Both serum and urine suPAR correlated with proteinuria and albuminuria. Serum suPAR was found to be elevated in all transplant candidates with advanced renal disease compared with healthy controls and could not differentiate disease diagnosis. Urine suPAR was elevated in cases of recurrent FSGS compared with all other causes of end-stage renal disease. Recurrent FSGS cases had substantially higher proteinuria compared with all other cases. However, elevated urinary suPAR showed a trend in providing additional prognostic information beyond proteinuria in the small cohort of recurrent FSGS cases. CONCLUSION: In advanced renal disease, elevated serum suPAR is not unique to FSGS cases. Urinary suPAR appears to be higher in cases of FSGS destined for recurrence and merits further evaluation.