Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level. METHODS: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants (ClinicalTrials.gov: NCT01206062). RESULTS: Over a median follow-up of 3.33 years (interquartile range 2.87-3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate <22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11-2.14, P = 0.01), compared with participants with bicarbonate 22-26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97). CONCLUSIONS: In hypertensive individuals, serum bicarbonate level <22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.

Effects of Intensive Systolic Blood Pressure Control on Kidney and Cardiovascular Outcomes in Persons Without Kidney Disease: A Secondary Analysis of a Randomized Trial.

BACKGROUND: The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear. OBJECTIVE: To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects. DESIGN: Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062). SETTING: Adults with high blood pressure and elevated cardiovascular risk. PARTICIPANTS: 6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. INTERVENTION: Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively). MEASUREMENTS: Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months. RESULTS: The difference in adjusted mean eGFR between the intensive and standard groups was -3.32 mL/min/1.73 m2 (95% CI, -3.90 to -2.74 mL/min/1.73 m2) at 6 months, was -4.50 mL/min/1.73 m2 (CI, -5.16 to -3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86). LIMITATION: Long-term data were lacking. CONCLUSION: Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effects of Intensive BP Control in CKD.

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

Favorable outcome of Fournier gangrene in two patients with diabetes mellitus on continuous peritoneal dialysis.

Fournier gangrene (FG), a form of necrotizing fasciitis of the perineum and genitals, with high morbidity and mortality in the general population, carries the additional risk of involvement of the peritoneal catheter tunnel and peritoneal cavity in patients on chronic peritoneal dialysis (PD). We describe two men with diabetes who developed FG in the course of PD. Computed tomography showed no extension of FG to the abdominal wall, and spent peritoneal dialysate was clear in both patients. Broad-spectrum antibiotic therapy with anaerobic coverage and early aggressive debridement followed by negative-pressure wound therapy and repeated debridement led to improvements in clinical status in both cases. Surgical closure and healing of the wound was achieved in one patient; the wound of the second patient is healing, but remains open. Both patients experienced prolonged hospitalization, with a serious decline in nutrition status. In patients on PD, FG can be treated successfully. However, additional measures are required to evaluate for potential involvement of the PD apparatus and the peritoneal cavity in the infectious process; and prolonged hospitalization, worsening nutrition, and multiple surgical interventions can result.

Blood Pressure Intervention and Control in SPRINT.

BACKGROUND: The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reductions in major cardiovascular disease events and mortality with an intensive systolic blood pressure (SBP) goal intervention. However, a detailed description of the blood pressure intervention, antihypertensive medication usage, blood pressure levels, and rates and predictors of blood pressure control has not been reported previously. METHODS: Hypertensive participants (n=9361) 50 years and older with elevated cardiovascular disease risk were randomized 1:1 to SBP goal <120 mm Hg or SBP goal <140 mm Hg. Guideline-recommended antihypertensive medications and dosing were provided at no cost. Intensive group participants were started on at least 2 medications, and medications were adjusted monthly until SBP goal was achieved, if feasible. Standard group participants were treated to achieve SBP 135 to 139 mm Hg. RESULTS: Baseline blood pressure (median±interquartile range) was 138±19/78±16 mm Hg. For intensive group participants, percent at goal rose from 8.9% at baseline to 52.4% at 6 months and average antihypertensive medications rose from 2.2 to 2.7; SBP was <120 mm Hg in 61.6% and <130 mm Hg in 80.0% at their final visit. For the standard group participants, percent at goal rose from 53.0% at baseline to 68.6% at 6 months, while antihypertensive medications fell from 1.9 to 1.8. From 6 to 36 months, median SBP was stable at 119±14 mm Hg for intensive and 136±15 mm Hg for standard participants, with stable numbers of medications. Few predictors of SBP control were found in multiple regression models. CONCLUSIONS: These results may inform and help replicate the benefits of SPRINT in clinical practice. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

Age, race, diabetes, blood pressure, and mortality among hemodialysis patients.

Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.

Sources of variation in estimates of lean body mass by creatinine kinetics and by methods based on body water or body mass index in patients on continuous peritoneal dialysis.

OBJECTIVE: We identified factors that account for differences between lean body mass computed from creatinine kinetics (LBM(cr)) and from either body water (LBM(V)) or body mass index (LBM(BMI)) in patients on continuous peritoneal dialysis (CPD). DESIGN: We compared the LBM(cr) and LBM(V) or LBM(BMI) in hypothetical subjects and actual CPD patients. PATIENTS: We studied 439 CPD patients in Albuquerque, Pittsburgh, and Toronto, with 925 clearance studies. INTERVENTION: Creatinine production was estimated using formulas derived in CPD patients. Body water (V) was estimated from anthropometric formulas. We calculated LBM(BMI) from a formula that estimates body composition based on body mass index. In hypothetical subjects, LBM values were calculated by varying the determinants of body composition (gender, diabetic status, age, weight, and height) one at a time, while the other determinants were kept constant. In actual CPD patients, multiple linear regression and logistic regression were used to identify factors associated with differences in the estimates of LBM (LBM(cr)LBM(V). The differences in determinants of body composition between groups with high versus low LBM(cr) were similar in hypothetical and actual CPD patients. Multivariate analysis in actual CPD patients identified serum creatinine, height, age, gender, weight, and body mass index as predictors of the differences LBM(V)-LBM(cr) and LBM(BMI)-LBM(cr). CONCLUSIONS: Overhydration is not the sole factor accounting for the differences between LBM(cr) and either LBM(V) or LBM(BMI) in CPD patients. These differences also stem from the coefficients assigned to major determinants of body composition by the formulas estimating LBM.

Imaging of peritoneal catheter tunnel infection using positron-emission tomography.

Imaging by ultrasonography or scintigraphy may assist in the diagnosis and management of tunnel infections of the peritoneal dialysis (PD) catheter. Here, we report a case of tunnel infection in which imaging with positron-emission tomography (PET) correctly predicted failure of conservative management. A 61-year-old man with diabetic nephropathy commenced PD in January 2008. He developed erythema and drainage at the exit site, with negative cultures in February 2008, and frank exit-site infection (ESI) with purulent drainage growing methicillin-sensitive Staphylococcus aureus [MSSA (treated with 3 weeks of oral dicloxacillin)] in August 2008. Subsequently, MSSA-growing purulent drainage from the exit site persisted. Systemic antibiotics were not administered, but there was gradual improvement with gentamicin ointment alone. In November 2008, the patient developed partial extrusion of the outer cuff of the PD catheter. In January 2009, a new ESI developed. Despite a week of treatment with cefazolin and gentamicin, the patient still developed his first episode of peritonitis with coagulase-negative Staphylococcus. He then received intraperitoneal vancomycin with good response. Although the ESI appeared to have responded to the treatment, PET imaging showed increased fludeoxyglucose (FDG) activity in the whole abdominal wall portion of the PD catheter. The patient resisted removal of the catheter and had no further signs of infection until June 2009. At that time he presented with exuberant inflammatory tissue ("proud flesh") at the exit site. Repeated PET imaging again showed increased FDG activity along the abdominal wall portion of the catheter. The PD catheter was removed and found to be infected. The patient was placed on temporary hemodialysis. This case demonstrates that PET imaging, in addition to other imaging techniques, may be useful for diagnosing and managing PD catheter infections.

Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Anemia management and association of race with mortality and hospitalization in a large not-for-profit dialysis organization.

BACKGROUND: The optimal hemoglobin target and possible toxicity of epoetin therapy in hemodialysis patients are controversial. Previous studies suggest that African American patients use higher doses of epoetin and have better survival compared with white hemodialysis patients. STUDY DESIGN: Retrospective longitudinal cohort. SETTING & PARTICIPANTS: Epoetin-exposed incident hemodialysis patients (N = 12,733; African Americans, n = 4,801; white, n = 7,386) treated in Dialysis Clinic Inc facilities during 2000 to 2006. PREDICTORS: Hemoglobin, epoetin, iron. OUTCOMES: Mortality, hospitalization. MEASUREMENTS: Proportional hazards models with time-varying covariates. RESULTS: Hemoglobin concentrations less than 10 g/dL in whites and less than 11 g/dL in African Americans were associated with increased mortality and hospitalization versus the referent hemoglobin level of 11 to 11.9 g/dL. Hemoglobin levels of 13 g/dL or greater in whites were associated with decreased noncardiovascular mortality. Six-month cumulative epoetin doses of 20,000 U/wk or greater were associated with increased mortality and hospitalization versus the referent group (8,000 to 12,499 U/wk). Epoetin doses less than 8,000 U/wk were associated with decreased risk. Higher epoetin doses were associated with increased mortality at hemoglobin concentrations of 10 to 12.9 g/dL and with increased hospitalization at all hemoglobin concentrations of 10 g/dL or greater. Higher epoetin doses were associated with increased mortality and hospitalization within each tertile of serum albumin concentration. These patterns did not differ by race. LIMITATIONS: Treatment-by-indication bias and unidentified confounders cannot be excluded. Small sample sizes in the highest and lowest hemoglobin strata decrease statistical power. CONCLUSIONS: Relationships between hemoglobin concentration and mortality differed between African Americans and whites. Additionally, the relationship of lower mortality with greater achieved hemoglobin concentration seen in white patients was observed for all-cause, but not cardiovascular, mortality. A higher cumulative epoetin dose was associated with worse outcomes, even in patients with albumin levels greater than 4 g/dL. There were no statistically significant interactions between race and epoetin dose. Further studies are needed to confirm and to define the mechanism of these findings.

Computerized decision support for EPO dosing in hemodialysis patients.

BACKGROUND: Anemia management in hemodialysis patients poses significant challenges. The present study explored the hypothesis that computerized dosing of intravenous erythropoietin (EPO) would increase the percentage of hemoglobin (Hb) values within the target range and reduce staff time spent on anemia management. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: In-center hemodialysis patients who received EPO at Dialysis Clinic Inc dialysis units for at least 3 months between October 1, 2005, and April 30, 2006. QUALITY IMPROVEMENT PLAN: Computerized decision support (CDS) for EPO dosing is compared with manual physician-directed dosing. OUTCOMES: Achieved monthly Hb values, quantity of EPO administered, and time spent by dialysis unit personnel. MEASUREMENTS: Monthly Hb and quantity of EPO administered to 1,118 patients from 18 dialysis units treated using CDS and 7,823 patients from 125 dialysis units treated using manual dosing. RESULTS: There was no difference in the likelihood of a monthly Hb level of 11-12 or 10-12 g/dL using CDS compared with manual dosing. The likelihood of an Hb level > 12 g/dL decreased and the likelihood of an Hb level < 10 g/dL increased using CDS. EPO use was 4% lower using CDS, although the difference was not statistically significant. CDS was associated with a nearly 50% decrease (P < 0.001) in the time spent by dialysis unit staff on anemia management. LIMITATIONS: Retrospective and nonrandomized. CONCLUSION: The number of monthly Hb values in an 11- (and 10-) to 12-g/dL target range and EPO use did not differ with EPO dosing using CDS compared with manual dosing. Staff resources devoted to anemia management decreased significantly using CDS.

Scrotal edema secondary to fluid imbalance in patients on continuous peritoneal dialysis.

In addition to local causes--for example, leak of dialysate into an inguinal hernia sac or into the anterior abdominal wall through the track of the catheter for continuous peritoneal dialysis (CPD)--scrotal edema in CPD patients may result from generalized volume retention. We present 2 CPD patients with scrotal edema, illustrating the diagnosis and management of the mechanisms of volume retention. A man with hypertensive nephrosclerosis developed isolated scrotal edema 14 months after an uneventful course of continuous ambulatory peritoneal dialysis (CAPD). After repair of a ventral hernia and of a communicating hydrocele, he started continuous cycling peritoneal dialysis (CCPD), plus 2 daytime CAPD exchanges. After 4 months, he again developed isolated scrotal edema, which decreased at night. Peritoneal scintigraphy showed no dialysate leaks, and peritoneal equilibration test (PET) revealed high-average transport with a residual volume above, and an ultrafiltration volume below, the expected range. Abdominal radiography revealed migration of the CPD catheter. Malposition of the CPD catheter with positional retention of dialysate was diagnosed. The patient was treated with nightly peritoneal dialysis and no daytime exchanges. On this regimen, ultrafiltration improved and the scrotal edema disappeared with no recurrence for 5 months, at which point the patient underwent kidney transplantation. A man with diabetic nephropathy developed poor dialysate return, volume gain, and pronounced edema of the scrotum, penis, and both legs soon after starting CAPD. Peritoneal scintigraphy was negative, and abdominal radiography confirmed the appropriate position of the CPD catheter tip in the right lower abdominal quadrant. PET revealed high peritoneal solute transport, appropriate residual volume, and appropriate for the transport category, but relatively low (0.1 L), ultrafiltration volume. He was treated with a change in the CPD procedure to CCPD, plus 1 daytime icodextrin exchange and instruction to reduce salt intake. This patient has remained free of scrotal edema for 6 months. In men on CPD, scrotal edema can develop from generalized volume gain secondary to either CPD catheter malfunction or imbalance between total fluid removal and salt and water intake. Proper interpretation of PET findings is critical in the evaluation of scrotal edema not resulting from internal dialysate leaks in CPD.

Hospitalizations in patients treated sequentially by chronic hemodialysis and continuous peritoneal dialysis.

It is not established whether hospitalizations are more frequent or longer in patients on peritoneal dialysis (PD) or chronic in-center hemodialysis (HD). Comorbidity is a major factor affecting the comparison of hospitalizations. To account for comorbidity, we compared hospitalizations between the PD and HD periods in 16 patients, 8 of whom were treated by PD first (group A), and 8, by HD first (group B). In group A, causes of renal failure were diabetes (n = 3), primary renal disease (n = 2), systemic disease (n = 2), and hereditary nephropathy (n = 1). Age at onset of PD was 53 +/- 11 years; duration of PD, 31 +/- 17 months; and duration of HD, 40 +/- 33 months. This group had 52 hospitalizations in the PD period and 80 hospitalizations in the HD period. Hospitalization rate (n/ patient-year) was 2.5 +/- 2.0 during PD and 3.0 +/- 3.0 during HD (nonsignificant), and duration of hospitalization (days/patient-year) was 19.6 +/- 15.5 during PD and 21.9 +/- 17.7 during HD (nonsignificant). The three most common causes of hospitalization were peritonitis (27%), other infections (21%), and cardiovascular disease (14%) in the PD period, and HD access problems (35%), infections (16%), and cardiovascular disease (12%) in the HD period. In group B, causes of renal failure were diabetes (n = 4), primary renal disease (n = 3), and hypertension (n = 1). Age at onset of HD was 56 +/- 10 years; duration of HD, 41 +/- 19 months; and duration of PD, 60 +/- 24 months. This group had 82 hospitalizations in the HD period and 76 hospitalizations in the PD period. Hospitalization rate was 3.0 +/- 2.4 during HD and 1.9 +/- 2.8 during PD (nonsignificant), and duration of hospitalization was 17.3 +/- 25.1 during HD and 12.7 +/- 21.3 during PD (nonsignificant). The three most common causes of hospitalization were HD access problems (40%), cardiovascular disease (19%), and infections (12%) in the HD period, and other infections (36%), cardiovascular disease (19%), and peritonitis (21%) in the PD period. In patients changing dialysis modalities, rate and duration of hospitalizations did not vary between HD and PD. The causes of hospitalization were similar in the HD and PD periods regardless of which modality was applied first.

Tumoral calcinosis without hyperparathyroidism in a patient on continuous ambulatory peritoneal dialysis.

Reports of tumoral calcinosis (TC) in peritoneal dialysis (PD) patients are rare. Reported PD patients with TC also had hyperparathyroidism. A 67-year-old man on continuous ambulatory PD for almost 3 years developed TC of the right wrist and knee and both shoulders and feet. In the 2 years preceding the diagnosis of TC, this patient's serum parathyroid hormone levels were consistently low (17 +/- 12 pg/ mL). Hypercalcemia had been found in 32% of the serum samples, hyperphosphatemia in 91%, and elevated Ca x P product in 78% of the samples. At presentation with TC, serum C-reactive protein was elevated, and serum levels of vitamin D compounds were below normal. Four months after the diagnosis of TC, the patient died with a combination of gastrointestinal and retroperitoneal bleeding episodes and septic events. Tumoral calcinosis may develop in PD patients without hyperparathyroidism. Sustained hyperphosphatemia and high Ca x P product are important in the pathogenesis of uremic TC. Elevated indices of inflammation may accompany TC. Studies are needed to identify other important factors in the pathogenesis of TC in PD patients and to evaluate treatment methods.

Glomerulonephritis causing acute renal failure during the course of bacterial infections. Histological varieties, potential pathogenetic pathways and treatment.

To illustrate diagnostic approaches, potential pathogenetic differences, epidemiological implications and therapeutic dilemmas posed by glomerulonephritis (GN) with acute renal failure (ARF) complicating bacterial infections, we analyzed the course of four male patients, aged 53-71 years, who developed GN and ARF following bacterial infections. The first two patients developed GN with immunoglobulin A (IgA) deposits after infections with hospital-acquired methicillin resistant Staphylococcus aureus (MRSA). Clinical, serologic and histological features, classification of GN and treatment differed between the two patients. In the first patient, serological features (transient hypocomplementemia, normal serum protein electrophoresis) and histological findings were consistent with typical post-infectious GN. Treatment with antibiotics alone resulted in normalization of the renal function despite the severity of ARF, which required temporary hemodialysis. In the second patient, serological features (normal serum complement, polyclonal elevation of gamma globulins) and histological picture of the kidneys were characteristic of IgA nephropathy with fibrocellular crescents, and skin histology was consistent with vasculitis. Cyclophosphamide and corticosteroids were added to the antibiotics, with partial improvement of the renal failure. The third patient developed simultaneous acute rheumatic fever and post-streptococcal GN causing severe ARF requiring hemodialysis. Complete recovery of ARF and migratory polyarthritis followed initiation of corticosteroids. The fourth patient developed ARF and cerebral vasculitis following a prolonged course of Streptococcus mutans endocarditis with delayed diagnosis. He also developed multiple serological abnormalities including elevated titers of antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), anti-phospholipid antibodies, rheumatoid factor, and modest hypocomplementemia. Kidney biopsy revealed ANCA-mediated focal GN with 10% crescents and acute interstitial nephritis. Treatment with cyclophosphamide plus corticosteroids, but not with antibiotics alone, resulted in resolution of both the ARF and the features of cerebral vasculitis. GN following bacterial infections may have various pathogenetic mechanisms, presents complex diagnostic challenges, may be preventable in the case of hospital-acquired MRSA, and, in addition to antibiotics, may require immunosuppressive therapy in carefully selected and monitored cases.

Syncope, Hypotension, and Falls in the Treatment of Hypertension: Results from the Randomized Clinical Systolic Blood Pressure Intervention Trial.

OBJECTIVE: To determine predictors of serious adverse events (SAEs) involving syncope, hypotension, and falls, with particular attention to age, in the Systolic Blood Pressure Intervention Trial. DESIGN: Randomized clinical trial. SETTING: Academic and private practices across the United States (N = 102). PARTICIPANTS: Adults aged 50 and older with a systolic blood pressure (SBP) of 130 to 180 mmHg at high risk of cardiovascular disease events, but without diabetes, history of stroke, symptomatic heart failure or ejection fraction less than 35%, dementia, or standing SBP less than 110 mmHg (N = 9,361). INTERVENTION: Treatment of SBP to a goal of less than 120 mmHg or 140 mmHg. MEASUREMENTS: Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were treatment assignment, demographic characteristics, comorbidities, baseline measurements, and baseline use of cardiovascular medications. RESULTS: One hundred seventy-two (1.8%) participants had SAEs involving syncope, 155 (1.6%) hypotension, and 203 (2.2%) falls. Randomization to intensive SBP control was associated with greater risk of an SAE involving hypotension (hazard ratio (HR) = 1.67, 95% confidence interval (CI) = 1.21-2.32, P = .002), and possibly syncope (HR = 1.32, 95% CI = 0.98-1.79, P = .07), but not falls (HR = 0.98, 95% CI = 0.75-1.29, P = .90). Risk of all three outcomes was higher for participants with chronic kidney disease or frailty. Older age was also associated with greater risk of syncope, hypotension, and falls, but there was no age-by-treatment interaction for any of the SAE outcomes. CONCLUSIONS: Participants randomized to intensive SBP control had greater risk of hypotension and possibly syncope, but not falls. The greater risk of developing these events associated with intensive treatment did not vary according to age.

Peritoneal dialysis as salvage renal replacement therapy after complete failure of hemodialysis access in an elderly patient with multiple comorbidities.

Although peritoneal dialysis (PD) has been advocated as a suitable substitution therapy in patients with failure of hemodialysis (HD) blood access, documentation of the performance of PD in such patients is limited. Here, we present an elderly patient with total failure of HD blood access who has had a remarkably successful course on PD. A 78-year-old man with several comorbidities started continuous ambulatory PD after a 3.5-year course of HD complicated by repeated vascular access infections and clotting episodes. These access complications resulted in 8 hospitalizations and led to inability to ambulate following a right femoral shaft fracture sustained in a fall secondary to confusion during an episode of access sepsis, and to superior vena cava (SVC) syndrome following SVC thrombosis after internal jugular catheter insertion. Over approximately 3 years, PD has been very successful in this patient, with 2 early routine episodes of peritonitis and 1 early episode of exit-site infection, control of hematologic and biochemical values, no hospitalizations in the 2.5 years before the time of writing, and good quality of life. A dedicated spouse performing the PD tasks has been a major factor in the success of PD in this patient. Peritoneal dialysis can be successful as a renal replacement procedure in incapacitated elderly patients with failure of HD blood access. In these cases, the success of PD is enhanced by dedicated family members taking on PD tasks that the patient cannot perform.

Computation of the dose of continuous peritoneal dialysis required for adequate peritoneal urea clearance without taking into account peritoneal transport indices.

To test the feasibility of calculating, in the absence of peritoneal transport studies, the dose (daily drain volume) of continuous peritoneal dialysis (CPD) that will produce a high probability of adequate fractional peritoneal urea clearance (Kpt/Vurea), we randomly separated 619 clearance studies in patients on continuous ambulatory peritoneal dialysis (CAPD) with 4 daily exchanges into a derivation (n = 322) and a validation (n = 297) group. In the derivation group, the dialysate-to-plasma urea concentration ratio (D/Purea) was < or = 0.799 within the lowest 5% of the studies. By the urea clearance formula, a D/Purea value of 0.799 will produce weekly Kpt/Vurea values of 1.70 or better if the ratio of the daily drain volume to plasma water (Dv/V) is > or = 0.304 L/L. Among the 56 studies in the validation group with Dv/V values of 0.304 L/L or more, 52 (92.9%) had weekly Kpt/Vurea values of 1.70 or better. Assuming a suitable (low) D/Purea value for a given CPD treatment, it is possible to derive the dose of dialysis (the Dv/V ratio) that will provide adequate peritoneal urea clearance levels regardless of peritoneal transport characteristics. This method is applicable to the prescription of CPD for patients lacking studies of peritoneal transport. Anuric patients on CAPD with 4 daily exchanges require a Dv/V value of 0.304 L/L or better to have a > or = 0.9 probability of achieving a weekly Kpt/Vurea of 1.70 or better.

Management of extreme azotemia from urinary tract obstruction without dialysis. Clinical correlates and kinetic modeling of the recovery of renal function.

The recovery of renal function following release of urinary tract obstruction with advanced azotemia determines both the need for emergency dialysis in the early post-obstructive period and the long-term planning for chronic kidney disease management. A man with prostatic cancer who presented with 16 days of anuria and a serum creatinine (Scr) of 42.7 mg/dl but had evidence suggesting residual renal function was managed conservatively and reached a steady-state Scr of 1.6 mg/dl within 84 h of urinary bladder catheterization. Modeling of the decrease in Scr taking into account the decline in the body creatinine pool that existed prior to the release of the obstruction and the accumulation in body fluids of creatinine produced after the release of the obstruction suggested that recovery of the value of glomerular filtration rate corresponding to the steady-state Scr occurred at the release of the urinary obstruction. The case illustrates both the clinical factors that may lead to the decision to postpone dialysis in a patient presenting with extreme obstructive azotemia and a novel method of modeling the recovery of renal function after release of the obstruction.

Near death by milk of magnesia.

We report a case of hypermagnesemia associated with the use of milk of magnesia in a male patient with end-stage renal disease. After experiencing nausea and vomiting, he developed severe bradycardia and then asystole. Resuscitation efforts were successful; however, he developed atrial fibrillation with severe widening of the QRS and diffuse ST elevation, hypothermia, hypotension and apnoea requiring intubation. Initial diagnoses included ST-elevation myocardial infarction, cardiogenic and/or septic shock and hyperkalaemia. However, serum magnesium was later found to be >4.1 mmol/L (equivalent to >10 mg/dL). He underwent haemodialysis (HD) to remove serum magnesium with remarkable overall improvement. Severe hypermagnesemia can manifest with severe bradycardia and asystole, shock, hypothermia and respiratory failure and can mimic acute coronary syndromes complicated with cardiogenic shock or septic shock. Therefore, clinicians should be aware of this life-threatening condition in patients with significant renal dysfunction. Timely treatment with HD is highly effective and lifesaving.