Chronic kidney disease in Ecuador: An epidemiological and health system analysis of an emerging public health crisis.

The absence of a chronic kidney disease (CKD) registry in Ecuador makes it difficult to assess the burden of disease, but there is an anticipated increase in the incidence of CKD along with increasing diabetes, hypertension and population age. From 2012, augmented funding for renal replacement therapy expanded dialysis clinics and patient coverage. We conducted 73 in-depth sociological interviews with healthcare providers in eight provinces and collected quantitative epidemiological data on patients with CKD diagnoses from six national-level databases between 2015 and 2018. Datasets show a total of 17,484 dialysis patients in 2018, or 567 patients per million population (pmp), with an annual cost exceeding 11% of Ecuador's public health budget. Each year, there were 139-162 pmp new dialysis patients, while doctors reported waiting lists. The number of patients on peritoneal dialysis was static; those on hemodialysis increased over time. Only 13 of 24 provinces were found to have dialysis services, and nephrologists were clustered in major cities, which limits access, delays medical attention, and adds a travel burden on patients. Prevention and screening programs are scarce, while hospitalization is an important reality for CKD patients. CKD is an emerging public health crisis that has increased dramatically over the last decade in Ecuador and is expected to continue, making coverage for all patients impossible and the current structure, unsustainable. A patient registry would help health policymakers and administrators estimate the demand and progression of patients with consideration for comorbidities, disease stage, requirements and costs, mortality and follow-up. This should be used to help identify where to focus prevention and improved treatment efforts. Organized monitoring of CKD patients would benefit from improvements in patient referral. Community-based education and prevention programs, the strengthening of primary healthcare capacity (including basic routine tests) and improved nephrology services are also urgently needed.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project.

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

Posterior reversible encephalopathy syndrome after renal transplant: a simple solution for a complicated patient.

BACKGROUND: Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by an acute neurologic dysfunction coupled with characteristic findings on brain imaging. PRES occurs in the setting of hypertensive emergencies, eclampsia and as a neurotoxic effect of immunosuppressive agents. While overwhelmingly reversible without residual deficits when promptly recognized, vague symptomatology may delay the diagnosis of PRES. RESULTS/SUMMARY: A 50-year-old man who had undergone a recent kidney transplant was admitted to our clinic due to multiple episodes of seizure. He had no prior history of seizures or alcoholism. His transplantation had been without complication; he was discharged and given prednisone, tacrolimus, mycophenolate, acyclovir, trimethoprim-sulfamethoxazole, atenolol and enalapril. On the day of presentation, he experienced a severe headache, blurred vision and tonic-clonic seizure-like activity. His neurologic examination was limited by sedation, although no focal deficits were evident. Laboratory studies were unremarkable. A lumbar puncture revealed normal opening pressure, negative Gram stain, benign CSF analysis and India ink preparation. An MRI of the brain revealed bilateral enhancing parietal-occipital lesions, seen prominently on FLAIR sequence. Tacrolimus and all other medications were continued. The patient remained afebrile and normotensive and was extubated on the second hospital day. The patient reported no neurologic symptoms and was discharged on the third hospital day after a full recovery. CONCLUSIONS: While the outcome of PRES is typically benign, a delay in diagnosis may lead to permanent neurologic deficits, and misdiagnosis can be lethal. The cornerstone of treatment is removal of the offending agent or treatment of the underlying etiology. A clinical picture of headache, visual abnormalities, altered mentation and seizures is sufficient to prompt an empiric discontinuation of agents known to cause PRES. Calcineurin inhibitors such as tacrolimus are known to cause PRES, and in our patient, discontinuation led to a complete clinical resolution.

Effect of simvastatin use on autonomic function in patients with end stage renal disease.

BACKGROUND: Heart Rate Variability (HRV) is a reliable measure of autonomic function. It is positively influenced by treatment with an HMG-CoA reductase inhibitor (statin) with resultant improvement in parasympathetic tone in the general hyperlipidemic population. We tested the hypothesis that autonomic function would improve following 4 weeks of treatment with a statin by conducting a randomized, double-blind, placebo-controlled, cross-over study in 10 subjects. METHODS: Stable subjects receiving chronic outpatient hemodialysis were enrolled without regard to lipid status. None of the subjects had received prior statin therapy. They spent the first four weeks of study taking either a placebo or simvastatin (40 mg po qD). They then switched to the other arm for the second four weeks. Measurements of inflammatory mediators and heart rate variability (HRV) were made at baseline and four week intervals. RESULTS: Absolute values of LDL values fell (>25%) with statin treatment. Highly sensitive C-reactive protein (hs-CRP), while demonstrating a trend to improvement, did not change significantly and was associated with a wide standard deviation as well as a baseline elevation well above normal values (baseline = 7.1 ± 6.7 mg/dL, ON statin = 10.8 ± 20.4 mg/dL, OFF statin = 6.9 ± 6.0 mg/dL, p > 0.05 = ns). None of the major time domains of HRV (SDNN, SDANN, RMSSD, or TRIA) responded to statin therapy in a statistically significant manner. Three of four domains did trend upward (indicating an increase in parasympathetic tone) following statin therapy. CONCLUSIONS: These data indicate that, unlike the general population, there is no statistically significant impact of statin use on autonomic function in patients on dialysis.

Chronic kidney disease, creatinine and cognitive functioning.

BACKGROUND: Non-dialysis-dependent chronic kidney disease (CKD) is related to cognitive impairment. Previous studies have not explored the extent of impairment across multiple cognitive domains. We examined the range of specific cognitive abilities affected by CKD and whether the associations of CKD with cognition were eliminated by statistical control for cardiovascular disease correlates of CKD. METHODS: We performed a community-based cross-sectional study with 923 individuals free from dementia and end-stage renal disease. Two groups were defined based on estimated glomerular filtration rate (eGFR): eGFR<60 mL/min/1.73 m(2) versus eGFR >or= 60 mL/min/1.73 m(2). Outcome measures were scores from multiple clinical tests of specific cognitive abilities. The GFR classifications and serum creatinine levels were related to measures of cognitive performance using logistic and linear regression analyses with three sets of covariates: (1) basic (age, education, gender and race); (2) basic+risk factors for cardiovascular disease (CVD) and (3) basic+risk factors for CVD+stroke. RESULTS: An eGFR <60 mL/min/1.73 m(2) was present in 142 (15.4%) individuals; the mean (SD) eGFR in this subgroup was 49.7 (10.7). CKD was related to lower cognitive performance despite adjustment for CVD risk factors (CVD-RF). Adjusting for CVD-RF and stroke, odds ratios and 95% confidence intervals associated with performing in the lowest quartile of the distribution of the Global, Visual-Spatial Organization/Memory and Scanning and Tracking scores for the eGFR < 60 group were 1.97 (1.25, 3.10); 1.88 (1.21, 2.93) and 1.83 (1.56, 2.87), P < 0.01 with eGFR >or= 60 group as the reference group. CONCLUSIONS: Global performance and specific cognitive functions are negatively affected early in CKD. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.

Influence of angiotensin converting enzyme inhibitor treatment on cardiac autonomic modulation in patients receiving haemodialysis.

BACKGROUND: Cardiovascular disease mortality among patients with end stage renal disease (ESRD) exceeds that which is predicted by traditional risk factors. Sudden death accounts for up to 15-38% of patients with ESRD found dead at home. Heart rate variability (HRV) is a reliable measure of autonomic modulation and has a very strong predictive value for ventricular arrhythmias and sudden death. A lower HRV is associated with increased risk. Modifying autonomic tone pharmacologically reduces death from dysrhythmia in the general population but has not been studied in ESRD. METHODS: We examined the effect of ramipril, an angiotensin converting enzyme inhibitor (ACEI) known in the general population to increase HRV, on cardiac function and heart rate variability in patients with renal failure. Eligible subjects on haemodialysis underwent a 2-week washout period free of ACEI or beta blockers, during which time hypertension was treated with amlodipine, which has been shown not to affect HRV. Haemodynamic and HRV measurements were obtained at baseline and after subjects were treated for 4 weeks with an ACEI. RESULTS: Haemodynamics did not differ at 0 and 4 weeks. Baseline HRV values were markedly below those found in the general population, indicating pronounced predominance of sympathetic tone over vagal tone. Actual worsening of HRV with ACEI treatment was evident in several major time domains. The time domain SDNN (the standard deviation of all normal RR intervals) fell from 42.0 +/- 24.8 ms to 20.1 +/- 16.1 ms (P = 0.004) and the triangulation index fell from 178.0 +/- 94.0 to 115 +/- 59.2 (P = 0.01). A trend toward reduced HRV was seen in several other time domains. CONCLUSION: These findings suggest that, unlike the general population, treatment of ESRD patients with an angiotensin converting enzyme inhibitor may cause a deleterious shift toward increased cardiac sympathetic nervous system tone.

Mechanisms of glomerular immune injury: effects of antioxidant treatment.

Significant glomerular vasoconstriction and production of reactive oxygen species has been known to occur with exposure to anti-glomerular basement membrane antibody (AGBM-Ab) in the rat model. Previously published studies have demonstrated that such effects can be reduced by therapy with phentolamine, an alpha-adrenergic antagonist. It was hypothesized that antioxidant pretreatment with water-soluble probucol would improve glomerular hemodynamics 60 to 90 min after the administration of AGBM-Ab. These relationships were examined with both in vivo renal micropuncture and in vitro studies in rats. Single-nephron GFR (SNGFR) decreased markedly in untreated rats after AGBM-Ab as a result of afferent and efferent arteriolar vasoconstriction with consequent reductions in nephron plasma flow (SNPF) and decreases in the glomerular ultrafiltration coefficient (LpA). Basal SNGFR was increased, and SNGFR was significantly higher after AGBM-Ab in probucol-treated versus untreated rats. This finding was due solely to higher values for SNPF and prevention of afferent arteriolar constriction. A reduction in LpA after AGBM-Ab was not prevented by probucol treatment. In vitro analyses of glomeruli revealed reduced myeloperoxidase activity in antioxidant-treated rats. Lipoxygenase activity and leukotriene products, however, were not changed by antioxidant therapy, yet vasoconstriction was prevented. H(2)O(2) generation before and after formyl-methionyl-leucyl-phenylalanine stimulation was significantly reduced before and after AGBM-Ab in glomeruli harvested from rats that were treated with the antioxidant. Antioxidant therapy in this model of AGBM-Ab injury did not prevent reductions in LpA, an index of glomerular membrane damage, but did prevent afferent arteriolar vasoconstriction. Reactive oxygen species generation was reduced by probucol. The specific mechanisms whereby antioxidant therapy ameliorates glomerular hemodynamic effects will be defined in additional studies and is likely to involve either enhanced vasodilator or diminished vasoconstrictor activity.

IgA nephropathy in a patient with chronic granulomatous disease.

We report the first documented case of X-linked chronic granulomatous disease (CGD) in association with IgA nephropathy in a 22 year old male with multiple soft tissue abscesses. The case highlights the potential role of staphylococcal infections in the pathogenesis of IgA nephropathy and suggests the hypothesis that the neutrophil defect in CGD predisposes to such infections which may trigger IgA immune complex formation.