Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.

Relative hypoparathyroidism and hypoalbuminemia are associated with hip fracture in hemodialysis patients.

AIMS: Patients with end-stage renal disease treated by hemodialysis are at an increased risk of hip fracture. In the general population, hip fractures are associated with increased morbidity and mortality. The objective of this study was to assess the predictors and outcomes of hip fracture in the hemodialysis population, including quality of life post hip fracture. METHODS: A case-control study from 1999 to 2005 included 29 adult hemodialysis patients with hip fracture and 55 controls, matched on age, gender and number of years on hemodialysis. A logistic regression model was used to derive predictors of hip fracture. The association between time to death post hip fracture and parathyroid hormone was analyzed using a Kaplan-Meier curve. The ability to live independently 1 year after hip fracture was used as a measure of quality of life. RESULTS: Variables associated with hip fracture were a reduction in serum parathyroid hormone by 100 pg/ml (OR = 1.65, 95% CI 1.10, 2.46) and a decrease in serum albumin by 1 g/l (OR = 1.18, 95% CI 1.00, 1.39). 40% of the cases died within the first year post hip fracture. Median survival time in patients with hip fracture and a serum PTH value < 100 pg/ml was 17 days (95% CI 0, 37 days) as compared with 280 days (95% CI 103, 471 days) for those with a PTH value > 100 pg/ml (p < 0.02). Among the patients who survived, 53% were subsequently discharged to a long-term care facility. CONCLUSIONS: Relative hypoparathyroidism and hypoalbuminemia are associated with an increased risk of hip fracture in hemodialysis patients. There is also a significant reduction in quality of life in patients sustaining a hip fracture.

Calcium antagonists and acute renal failure.

PURPOSE: To critically review the question of whether calcium antagonists can prevent or attenuate post-ischemic acute renal failure (ARF). PATIENTS AND METHODS: Using a computer-assisted search, we identified all experimental and clinical studies published in English between 1980 and 1988 in which the main research question addressed the efficacy of verapamil, diltiazem, or nifedipine in the treatment of post-ischemic ARF. Studies were then selected for review based on clearly specified inclusion criteria and evaluated against accepted methodologic guidelines. RESULTS: In experimental studies of warm renal ischemia, calcium antagonists provided significant protection of glomerular filtration rate (GFR) when given before and after ischemic injury; however, isolated pre- or post-ischemic treatment produced equivocal results. In autotransplantation studies on protracted cold ischemia, verapamil produced a modest, although physiologically significant, increase in GFR during warm reperfusion but failed to alter graft survival. Studies of calcium antagonists in humans with ARF have been confined to patients undergoing renal transplantation. Diltiazem given both to donor grafts and to recipients produced a significant reduction in the rate of delayed graft function but failed to improve one-year graft survival. This result may be due to the study of small numbers of low-risk patients. At present, there is no conclusive evidence that one calcium antagonist is more efficacious than another in the treatment of post-ischemic ARF. CONCLUSIONS: Calcium antagonists appear to prevent or reduce the severity of post-ischemic ARF only when given prior to and after the ischemic insult. As a result, these agents will have most utility in the setting of renal transplantation. Although the efficacy of these agents in reducing delayed graft function appears to be established, their failure to improve graft survival is poorly understood and requires further investigation.

The quality of life in renal transplantation--a prospective study.

Methodologically sound measures of quality of life are required to judge accurately the impact of successful renal transplantation on patient well-being. The time trade-off (TTO) method is a reproducible and valid measure which we used to prospectively assess changes in the quality of life of 27 patients on maintenance dialysis who subsequently underwent renal transplantation. TTO scores approaching 0 signify a very poor quality of life, while scores approaching 1 represent perfect health. Of 98 dialysis patients who completed baseline TTO interviews, 31 consecutive patients subsequently received 28 cadaveric and 3 living related kidney transplants. Four of 31 patients did not complete a second TTO assessment, because of death in 2 patients and graft loss in 2 others. The remaining 27 patients completed a second TTO interview an average of 30.9 months following transplantation (range 1.5-52, 95% confidence interval [CI] 24.4-37.5) and formed the study cohort. At the time of study the mean serum creatinine for the cohort was 173 mumol/L (range 90-290, 95% CI 152-195 mumol/L). The employment rate rose 27% following transplantation (P = 0.10); but when males alone were analyzed, a significant increase of 38% (P = 0.048) was noted. During the dialysis period, the mean baseline TTO score was 0.41 (95% CI 0.33-0.49), confirming the observations of others. Following transplantation, the mean TTO score rose to 0.74 (95% CI 0.67-0.81), a difference that is statistically significant (P < 0.001). The mean increase in TTO score observed as a result of successful transplantation was 0.33 (95% CI 0.26-0.40). This magnitude of improvement was found in 20 of 27 patients (74%), whose TTO scores lay within or above the 95% CI (0.26-0.40) for the mean change in score of 0.33. One patient's score fell, while the remaining 6 patients had improvements in their TTO score which fell below the lower 95% CI value (0.26) for the mean change in score. We conclude that the 95% CI of 0.26-0.40 identifies a range in which clinically important improvements in quality of life will be found for the majority of patients receiving successful kidney transplants.

Research directions: new clinical frontiers.

One of the greatest remaining challenges facing nephrology research is obtaining data with detail and precision for the three large, yet "forgotten," populations that span the spectrum of kidney disease: patients with chronic renal insufficiency (CRI), peritoneal dialysis patients, and kidney transplant patients. Studies of these populations, particularly the CRI group, are hampered by the relative mobility of these patients, the lack of stringent epidemiologic or clinical definitions, and the tendency to extrapolate data from hemodialysis populations into other clinical settings. This article suggests a two-pronged approach to a research agenda: first, by recognizing the need for better data regarding the natural history of these kidney failure subsets and their comorbidities; and second, by directing greater effort at identifying rational, efficacious, and cost-effective interventions to influence their natural history positively. Specific efforts are suggested in all three populations. For patients with CRI, studies should be directed at (1) identifying high-risk patients; (2) determining methods for making optimal referrals to the nephrologist; (3) identifying and managing CRI, its complications, and its comorbid conditions; and (4) establishing processes for the smooth transition to dialysis. The peritoneal dialysis population will benefit from studies addressing the treatment of anemia and its ability to modify cardiovascular illness and quality of life. Kidney transplant studies should also focus on the identification and management of comorbid conditions, as well as the effects of various interventions on quality of life. Rational evidence-based care of these conditions, which are critically important to patients, their families, and the health care system in general, must await the conduct of well-designed prospective observational and interventional trials.

Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling.

Few reports are available on the age-related risk of relatives of affected persons to manifest adult polycystic kidney disease (APKD). For 371 persons in 17 kindreds, at risk for APKD by virtue of having an affected first degree relative, we calculated the estimated probability of clinical diagnosis of APKD to be 0.011 by age 20, 0.041 by age 30, 0.115 by age 40, 0.299 by age 50, and 0.404 by age 60 years (expected = 0.50). Ultrasonographic examination of 172 asymptomatic persons at risk showed definite APKD in 60. The probability of ultrasonographic detection of asymptomatic APKD is estimated as 0.222, 0.657, and 0.855 at age 5, 15, and 25 years, respectively. The probability of having APKD following normal ultrasonogram results (conservatively assuming 90% specificity) is estimated as 0.46, 0.28, and 0.14 for persons at 50% risk in their first, second, or third decade. The marginal benefit of ultrasound as a diagnostic test for APKD for persons in the second or third decade is estimated as 0.37 and 0.41, respectively for a "positive" test and 0.22 and 0.37 for a "negative" test.

Renal disease-a sixth cardinal feature of the Laurence-Moon-Biedl syndrome.

A 39 year old man with 4 of the 5 cardinal features of the Laurence-Moon-Biedl syndrome (LMBS) had proteinuria and moderate renal failure. Excretory urography showed small cysts communicating with the dilated calyceal system. Renal biopsy showed diffuse mesangial sclerosis and cellular proliferation. Excretory urograms in 22 of 24 reported patients demonstrated similar findings. Review of renal pathology reports on 16 patients revealed either chronic glomerulonephritis or severe tubulo-interstitial disease with cysts or both in 8 of 9 who died from uremia and 2 of 7 who died from other causes. The abnormalities seen on excretory urography occur more frequently than 2 of the cardinal features, and as uremia is often the cause of death for these patients, renal disease should be considered a cardinal feature of LMBS.

Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients.

The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history. These patients had not been prescribed EPO as they had started hemodialysis prior to the clinical availability of EPO. There were 21 pairs without hospitalization and 46 pairs with at least 1 member of the pair experiencing hospitalization. Among the latter group, the median follow-up was 174 and 184 days for the EPO and control patients respectively. For all hospitalizations, those treated with EPO were hospitalized 15.3 days per year compared to 23.2 days for the control patients. The difference (EPO-control) was -7.9 days (95% CI: -21.0; 7.8) for all cause hospitalization. For hospitalizations due to cardiac, infectious disease and gastrointestinal disease, the differences were 1.6, 1.8 and 1.2 days favouring EPO treated patients. For hospitalizations related to vascular access complications, the difference was 0.9 days favoring the control group. All other causes favoured EPO treated patients by 4 days. There had been 58 hospitalizations in the EPO group compared to 97 in the control group. The mean duration of hospitalization was 8.0 days for the EPO and 9.6 for the control group. The direction and magnitude of the change in all cause hospitalization represents an improvement in morbidity and an important decrease in health resource utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome studies in adequacy of dialysis.

The theoretical constructs indicate that for a 70-kg high transport anephric patient, adequate dialysis requires a weekly Kt/V of 2.0-2.25. The prospective cohort studies, with one exception, suggest that better survival requires a weekly Kt/V > 1.89. Multivariate analyses confirm the statistical association of patient survival with higher Kt/V and with higher CCr. The use of initial values in one study, mean values in two studies, and time-dependent values in another makes comparison difficult. In general, higher values are associated with better survival and are consistent with the values suggested by theoretical constructs (i.e., Kt/V 2.0-2.25).

Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis (CAPD).

Ten adult patients on continuous ambulatory peritoneal dialysis (CAPD) received one dose of trimethoprim-320 mg (TMP) and sulfamethoxazole 1600 mg (SMX) orally (p.o.), intravenously (i.v.), and intraperitoneally (i.p.) on three separate occasions to characterize the pharmacokinetics of both drugs. Concentrations of both TMP and SMX were measured in serum and dialysate by HPLC to 48 h. Half-life, total body clearance (TBC), and peritoneal clearance (PCl) were determined. The mean half-life of TMP was 28 h, while for SMX it was 12.5 h. Relative to the i.v. dose, the bioavailability following oral administration for TMP was 98% and 87% for SMX. Intraperitoneal bioavailability was 73% for TMP and 65% for SMX after a 4-h dwell. After 24 h, regardless of the route of administration, less than 3% of TMP and less than 6% of SMX appeared in dialysate. We conclude that peritoneal losses contribute insignificantly to TMP/SMX elimination during CAPD.

Peritoneal membrane transport and hypoalbuminemia: cause or effect?

OBJECTIVE: Peritoneal membrane transport has been associated with serum albumin and clinical outcome. We examined the relationship between serum albumin and peritoneal membrane transport status before and after the initiation of peritoneal dialysis. SETTING: Patients were followed at a tertiary-care regional nephrology program at St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. METHODS: Incident peritoneal dialysis patients between 1 January 1995 and 31 May 1998 were eligible if there was a peritoneal equilibration test within 180 days of starting dialysis, and a serum albumin value measured within 90 days prior to, and 20 to 70 days after initiating dialysis. MAIN OUTCOME MEASURES: Serum albumin, before and after the initiation of dialysis, and the presence of proteinuric renal disease were compared with the peritoneal equilibration test results. RESULTS: Among 67 identified patients, there were 7 high, 27 high-average, 26 low-average, and 7 low transporters and the mean serum albumin values before dialysis were 35.1, 37.4, 37.8, and 40.4 g/L, respectively (p < 0.001). Serum albumin values prior to the initiation of dialysis correlated significantly with the 4-hour D/P creatinine ratio (r = -0.251, p = 0.040). After initiation of dialysis, the correlation was stronger (r= -0.447, p< 0.001). Serum albumin prior to initiation of dialysis was lower for those with proteinuric than nonproteinuric renal disease (36.4 g/L vs 38.8 g/L, p = 0.04). The trend to lower serum albumin in high transporters was seen in patients with both proteinuric and nonproteinuric renal disease. CONCLUSION: The association between higher peritoneal membrane transport and lower serum albumin is present before initiation of dialysis in both proteinuric and nonproteinuric renal disease. The poor outcomes associated with low serum albumin and higher peritoneal membrane transport might be explained by other underlying factors. The contribution of inflammation, malnutrition, and fluid overload requires further study.

Solute clearance approach to adequacy of peritoneal dialysis.

To investigate the effect of dialysis prescription on patient outcome for peritoneal dialysis patients, the relationship between total solute clearance and the relative risk of death has been investigated. Preliminary studies have suggested that more clearance is better and that patient outcome is predicted by total solute clearance. The recently published Canada-U.S.A. (CANUSA) multicenter study, evaluating adequacy of dialysis and nutrition in peritoneal dialysis patients, has further defined this relationship. Although these publications allow us to establish guidelines for the treatment of peritoneal dialysis patients, they also define the limitation of our knowledge and raise new questions. In this article we review our current knowledge regarding the predicted value of total solute clearance with patient outcome and nutritional status. Furthermore, we attempt to outline a practical approach for optimizing total solute clearance in peritoneal dialysis patients. Based on a review of the published literature and clinical recommendations, we feel that the minimal target total solute clearance for continuous forms of peritoneal dialysis is a weekly total KT/V > 2.0 and/or a weekly total creatinine clearance > 60 L/week/1.73 m2. For intermittent therapies, a weekly total KT/V > 2.2 and/or a weekly total creatinine clearance > 70 L/week/1.73 m2 is recommended.

Recommended clinical practices for maximizing peritoneal dialysis clearances.

Data from the Canada-U.S.A. (CANUSA) Study have recently confirmed a long-suspected linkage between total clearance and patient survival in peritoneal dialysis (PD). Recognizing that what we have historically accepted as adequate PD simply is not, the Ad Hoc Committee on Peritoneal Dialysis Adequacy met in January, 1996. This committee of invited experts was convened by Baxter Healthcare Corporation to prepare a consensus statement that provides clinical recommendations for achieving clearance guidelines for peritoneal dialysis. Through an analysis of 806 PD patients, the group concluded that adequate clearance delivered with PD can be achieved in almost all patients if the prescription is individualized according to the patient's body surface area, amount of residual renal function, and peritoneal membrane transport characteristics. Use of 2.5 L to 3.0 L fill volumes, the addition of an extra exchange, and giving automated peritoneal dialysis patients a "wet" day are all options to consider when increasing weekly creatinine clearance and KT/V. Rather than specify a single clearance or KT/V target, the recommended clinical practice is to provide the most dialysis that can be delivered to the individual patient, within the constraints of social and clinical circumstances, quality of life, life-style, and cost. The challenge to PD practitioners is to make prescription management an integral part of everyday patient management. This includes assessment of peritoneal membrane permeability, measurement of dialysis and residual renal clearance, and adjustment of the dialysis prescription when indicated.