Marcos Rothstein

Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is often characterized by end-stage renal disease (ESRD) and problems including pain, hematuria, and infection. Open nephrectomy is curative; however, the morbidity of the procedure is considerable. Between 1995 and 1998, 11 laparoscopic nephrectomies were performed on nine symptomatic patients (five men and four women) with ESRD and ADPKD. Two patients underwent a staged bilateral laparoscopic nephrectomy. All patients presented with abdominal or flank pain and an abdominal mass. Other clinical problems included hypertension in eight patients, urinary tract infections in two patients, and gross hematuria in one patient. Seven patients were receiving long-term dialysis treatment, and two patients had undergone prior renal transplantation. Patients were evaluated for preoperative and postoperative pain, analgesic use, hospital course, and convalescence. The overall average operative time was 6.3 hours, with an average estimated blood loss of 153 mL. Eight nephrectomy specimens were removed by morcellation, and three specimens were removed intact through a 7- to 12-cm incision. The average hospital stay was 3 days, and the average time to normal activity was 5 weeks. With a mean follow-up of 31 months, all nine patients reported elimination of their preoperative pain based on a pain analogue score. Six major and two minor complications occurred, including blood transfusion, a vena cavotomy, splenic cyanosis, pulmonary embolism, clotted arteriovenous fistula, and brachial plexus injury. Incisional hernias occurred in two of the three patients who underwent open removal. One patient noted improvement, and two patients noted resolution of their hypertension postoperatively. Laparoscopic nephrectomy in patients with ADPKD and ESRD offers an effective alternative to open nephrectomy to manage renal-related pain. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay, and rapid convalescence.

Tuberculosis infection and anergy in hemodialysis patients

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.

FGF-23 and sFRP-4 in Chronic Kidney Disease and Post Renal Transplantation

Background: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associated with chronic kidney disease (CKD) or in the hypophosphatemia associated with renal transplants. Methods: Plasma FGF-23, FRP-4, phosphorus and parathyroid hormone were measured in patients at all stages of CKD. Phosphate regulation of FGF-23 and secreted frizzled related protein-4 (sFRP-4) was examined in end-stage renal disease patients in the presence and absence of therapeutic phosphate binder usage. In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4–5 days after transplantation. Results: Plasma FGF-23 correlated with creatinine clearance (r2 = –0.584, p < 0.0001) and plasma phosphorus (r2 = 0.347, p < 0.001) in CKD patients and with plasma phosphorus (r2 = 0.448, p < 0.001) in end-stage renal disease patients. Phosphate binder withdrawal increased FGF-23 levels. In kidney transplant patients, dramatic decreases in FGF-23 (–88.8 ± 5.4%) and phosphorus (–64 ± 10.2%) were observed by 4–5 days post-transplantation. In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r2 = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia. Conclusions: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting FGF-23 is cleared by the kidney. Residual FGF-23 may contribute to the hypophosphatemia in post-transplant patients.

Vascular access thrombosis in new hemodialysis patients

This study identifies factors that are associated with the risk of access thrombosis in 267 new hemodialysis patients. There are few longitudinal studies evaluating the risk of access thrombosis despite the need for long-term use of the access for maintenance hemodialysis. We used a prospective design following patients from 26 providers in Renal Network Council #12 (Iowa, Missouri, Kansas, and Nebraska) for 1 year who were starting hemodialysis. There were significant increases in access thrombosis relative risk (RR) associated with the placement of a polytetrafluoroethylene graft compared with patients with the arteriovenous fistula (RR 1.98; 95% confidence interval [CI] = 1.3, 3,01). The probability of remaining thrombosis free 90 days after first use was 90.1% (95% CI = 82.9, 94.4) for arteriovenous fistula patients, but only 71.6% (95% CI = 63.5, 78.2) for polytetrafluoroethylene graft patients. In arteriovenous fistula patients with more than 30 days maturity time the risk of thrombosis was significantly lower than in those with less maturity time (RR 0.40; 95% CI = 0.14, 0.84); however, there was no significant difference for maturity time among patients with a polytetrafluoroethylene graft. Reduced thrombosis risk also was observed in patients with dialyzer blood flow rates greater than 300 mL/min (RR 0.66; 95% CI = 0.44, 0.99). Total heparin dose and erythropoietin therapy were not associated with the risk of thrombosis. No differences in risk were found for age, renal diagnosis, or type of dialyzer.

Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease

Background/Aims: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. Methods: We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results: There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. Conclusion: Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

Endothelin-1 release by erythropoietin involves calcium signaling in endothelial cells

We investigated the effects of recombinant human erythropoietin (rHuEPO) on intracellular calcium ([Ca2+]i) and whether these changes regulate both endothelin-1 (ET-1) protein release and ET-1 messenger RNA (mRNA) production in bovine pulmonary arterial endothelial cells (BPAEC). rHuEPO (3.3 U/ml) induced [Ca2+]i increases from a basal level of 54 +/- 12.2 (SE) to 147 +/- 21.1 nM (p < 0.001), in fura-2-loaded BPAEC. In the presence of nifedipine (10 microM), the increases in [Ca2+]i were significantly reduced. Furthermore, when extracellular calcium ([Ca2+]o) was reduced (200 microM), there was a significant reduction in [Ca2+]i increase after stimulation with rHuEPO. Incubation of BPAEC with rHuEPO for 4 h increased ET-1 levels in the culture supernatant from 44.7 +/- 5.3 to 85 +/- 7.6 pg/ml (p < 0.001). However, when the cells were treated with rHuEPO and nifedipine, the ET-1 levels were decreased, as compared to levels resulting from treatment with rHuEPO alone (41 +/- 6.1 vs. 85 +/- 7.6 pg/ml, p < 0.001, respectively). rHuEPO also induced a fourfold increase in the level of the preproET-1 mRNA as compared with control. PreproET-1 mRNA was diminished in the presence of nifedipine and rHuEPO and rHuEPO can increase [Ca2+]i in BPAEC, and this increase may be related to the stimulation of ET-1 synthesis and release.

A Crossover Intervention Trial Evaluating the Efficacy of a Chlorhexidine-Impregnated Sponge in Reducing Catheter-Related Bloodstream Infections among Patients Undergoing Hemodialysis

BACKGROUND Catheter-related bloodstream infections (CRBSIs) account for the majority of hemodialysis-related infections. There are no published data on the efficacy of the chlorhexidine-impregnated foam dressing at reducing the rate of CRBSI among patients undergoing hemodialysis. DESIGN A prospective, nonblinded, crossover intervention trial to determine the efficacy of a chlorhexidine-impregnated foam dressing to reduce the rate of CRBSI among patients undergoing hemodialysis. SETTING Two outpatient dialysis centers. PATIENTS A total of 121 patients who underwent dialysis through tunneled central venous catheters received the intervention during the trial. METHODS The primary outcome of interest was the incidence of CRBSI. A nested cohort study of all patients who received the chlorhexidine-impregnated foam dressing was also conducted. Backward stepwise logistic regression analysis was used to determine independent risk factors for development of CRBSI. RESULTS Thirty-seven CRBSIs occurred in the intervention group, for an incidence of 6.3 CRBSIs per 1,000 dialysis sessions, and 30 CRBSIs occurred in the control group, an incidence of 5.2 CRBSIs per 1,000 dialysis sessions (risk ratio, 1.22 [95% confidence interval {CI}, 0.75-1.97]; P = .46). The chlorhexidine-impregnated foam dressing was well tolerated, with only 2 patients (<2%) experiencing dermatitis that led to its discontinuation. The only independent risk factor for development of CRBSI was dialysis treatment at one dialysis center (adjusted odds ratio, 4.4 [95% CI, 1.77-13.65]; P = .002). Age of at least 60 years (adjusted odds ratio, 0.28 [95% CI, 0.09-0.82]; P = .02) was associated with lower risk of CRBSI. CONCLUSIONS The use of a chlorhexidine-impregnated foam dressing did not decrease the incidence of CRBSI among patients with tunneled central venous catheters who were undergoing hemodialysis.

Dialysis enrollment patterns in Guatemala: evidence of the chronic kidney disease of non-traditional causes epidemic in Mesoamerica

BackgroundIn western Nicaragua and El Salvador, chronic kidney disease (CKD) is highly prevalent and generally affects young, male, agricultural (usually sugar cane) workers without the established CKD risk factors. It is yet unknown if the prevalence of this CKD of Non-Traditional causes (CKDnT) extends to the northernmost Central American country, Guatemala. Therefore, we sought to compare dialysis enrollment rates by region, municipality, sex, daily temperature, and agricultural production in Guatemala and assess if there is a similar CKDnT distribution pattern as in Nicaragua and El Salvador.MethodsThe National Center for Chronic Kidney Disease Treatment (Unidad Nacional de Atención al Enfermo Renal Crónico) is the largest provider of dialysis in Guatemala. We used population, Human Development Index, literacy, and agricultural databases to assess the geographic, economic, and educational correlations with the National Center for Chronic Kidney Disease Treatment’s hemodialysis and peritoneal dialysis enrollment database. Enrollment rates (per 100 000) inhabitants were compared by region and mapped for comparison to regional agricultural and daytime temperature data. The distribution of men and women enrolled in dialysis were compared by region using Fisher’s exact tests. Spearman’s rank correlation coefficients were calculated.ResultsDialysis enrollment is higher in the Southwest compared to the rest of the country where enrollees are more likely (p < 0.01) to be male (57.8%) compared to the rest of the country (49.3%). Dialysis enrollment positively correlates with Human Development Index and literacy rates. These correlations are weaker in the agricultural regions (predominantly sugar cane) of Southwest Guatemala.ConclusionsIn Guatemala, CKDnT incidence may have a similar geographic distribution as Nicaragua and El Salvador (higher in the high temperature and sugar cane growing regions). Therefore, it is likely that the CKNnT epidemic extends throughout the Mesoamerican region.

Left ventricular mass progression despite stable blood pressure and kidney function in stage 3 chronic kidney disease.

Background/Aims: Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods: We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters2.7 (LVM/Ht2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). Results: Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht2.7 increased (47 ± 13 vs. 53 ± 13 g/m2.7, p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht2.7 (r2 = 0.582, p = 0.03). Conclusion: Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers.

Lack of influence of 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion from normal or hyperplastic glands

SummaryThe role of 24,25(OH)2D3 on parathyroid gland function remains controversial. The present studies were performedin vitro using (a) dispersed normal bovine parathyroid cells (bPTC) and (b) dispersed canine PTC (cPTC) prepared from glands of normal dogs, dogs with chronic renal failure (CRF), and dogs with CRF treated with 24,25(OH)2D3, 2.5 µg orally every day for more than 6 months. Bovine parathyroid cells were incubated for up to 180 min at 0.5, 1.0, and 3.0 mM external calcium in the presence or absence of 24,25(OH)2D3 (100 or 1000 nM). Similar experiments were conducted with cells incubated for 24 h in the presence of either the ethanol vehicle or 24,25(OH)2D3 (1000 nM). Parathyroid hormone secretion, measured in the supernatant by both C-terminal and N-terminal assays, did not show any differences between control and experimental groups at any time interval. Canine parathyroid cells obtained from uremic animals showed an average threefold increase in the total amount of PTH secreted, on a per cell basis over 180 min at 0.5 mM Ca2+, when compared with normal controls. However, there was no significant difference in PTH secretion at any level of calcium concentration between the cells obtained from parathyroid glands of CRF dogs and 24,25(OH)2D3-treated CRF dogs. Acute exposure to 24,25(OH)2D3 (1000 nM)in vitro of the cells obtained from the glands of CRF dogs also had no effect on PTH secretion. We conclude that 24,25(OH)2D3 has no direct effect on PTH secretion from dispersed parathyroid cells of either normal or uremic animals.