Alan S. Kliger

In-center hemodialysis six times per week versus three times per week

BACKGROUND In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis. METHODS Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access. RESULTS Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents. CONCLUSIONS Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Comparing the Risk for Death with Peritoneal Dialysis and Hemodialysis in a National Cohort of Patients with Chronic Kidney Disease

Context Does dialysis method affect survival of patients with end-stage renal disease? Contribution At 81 clinics in 19 states, 25% of the patients receiving peritoneal dialysis and 5% of those receiving hemodialysis switched methods at least once within 7 years. Patients initiating treatment with peritoneal dialysis appeared healthier and of higher socioeconomic status than did those receiving hemodialysis. Analyses that adjusted for baseline differences found statistically significantly higher risks for death among patients receiving peritoneal dialysis compared with those receiving hemodialysis during the second, but not first, year of treatment. Cautions This prospective study of incident dialysis was not a randomized trial. The Editors The burden of end-stage renal disease (ESRD) in the United States has increased dramatically over the past 30 years, with the number of patients treated for ESRD with dialysis or transplantation reaching more than 400000 by the end of 2001 (1). The number of patients requiring renal replacement therapy is projected to exceed 2 million patients by 2030 (1). Although kidney transplantation remains the best treatment option for eligible patients with ESRD (2), rates of kidney donation have not kept pace with the number of cases, leading to an increase in the number of patients on waiting lists (1). Thus, most patients with ESRD, including those eligible for kidney transplantation, must select a type of dialysis for renal replacement therapy. Since the introduction of peritoneal dialysis in the mid-1970s, several studies have tried to assess differences in survival between patients undergoing peritoneal dialysis and those undergoing hemodialysis, but the influence of type of dialysis on survival of patients with ESRD or subgroups of these patients remains controversial. Limitations of previously published studies include the enrollment of patients who had been receiving dialysis therapy for different amounts of time after the onset of ESRD (3), noncontemporary cohorts of patients undergoing incident dialysis (3-6), short follow-up (1 to 2 years) (3, 7-12), and limited information on comorbid conditions (3, 6, 7, 9, 13). Furthermore, many of these studies used only intention-to-treat analyses that do not account for switches in type of dialysis that occur over time (3-5, 7-9, 13). We performed a comprehensive comparative study of survival in patients undergoing peritoneal dialysis and those undergoing hemodialysis. Methods Study Design and Sample We conducted a national prospective cohort study of patients undergoing incident dialysis. Eligibility criteria for enrollment into the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study included ability to provide informed consent for participation, age older than 17 years, and ability to speak English or Spanish. Median time from initiation of dialysis to enrollment was 45 days; 98% of patients enrolled within 4 months of initial dialysis. Enrolled patients were oversampled for peritoneal dialysis to allow statistical comparisons by type of dialysis The institutional review boards of Johns Hopkins University and the clinical centers approved the study protocol, and all participants gave written informed consent. From October 1995 to June 1998, 1041 participants from 19 U.S. states were enrolled at 81 dialysis clinics associated with Dialysis Clinic, Inc., Nashville, Tennessee (923 patients), and New Haven Continuous Ambulatory Peritoneal Dialysis (86 patients) or St. Raphaels Hospital, New Haven, Connecticut (32 patients). Data Collection Demographic and Clinical Data At baseline, patients used a questionnaire to self-report demographic characteristics, health behaviors, work history, medical history, preparation for dialysis, social support, and distance to dialysis unit. Baseline data on routine care were available for serum albumin level, hemoglobin level, calcium-phosphate product, and total cholesterol level. High-sensitivity C-reactive protein was measured at a median of 5.0 months from initiation of dialysis by using a colorimetric competitive enzyme-linked immunosorbent assay (coefficient of variation, 8.9%). Residual urine output was defined as the ability to produce at least 250 mL of urine daily; this information was obtained from the baseline self-report questionnaire. Glomerular filtration rate before initiation of dialysis was estimated from the Modification of Diet in Renal Disease equation by using the serum creatinine concentration obtained from the ESRD Medical Evidence Report (Form 2728) (14). Dialysis Technique Dialysis technique at baseline was defined as the type of dialysis being used at 4 weeks after enrollment in the study (an average of 10 weeks after starting dialysis) and was obtained from clinic records. All forms of peritoneal dialysis (continuous ambulatory peritoneal dialysis, continuous cycling peritoneal dialysis, and intermittent cycling peritoneal dialysis) were combined as a single category. Patients were considered to have switched technique when they changed from one type of dialysis to another and continued to use the new technique for at least 30 days. Assessment of Comorbid Conditions Comorbid conditions were assessed by using the Index of Coexistent Disease, a medical recordderived index that has been demonstrated to predict death in patients undergoing dialysis (15, 16). Scores on this index range from 0 (no comorbid condition) to 3 (highest severity of comorbid conditions). The Index of Coexistent Disease aggregates the presence and severity of comorbid conditions within 2 scales: the Index of Disease Severity and the Index of Physical Impairment. The Index of Disease Severity consists of 19 categories of medical conditions (ischemic heart disease, congestive heart failure, arrhythmias, other heart disease, hypertension, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, respiratory disease, cancer, hepatobiliary disease, gastrointestinal disease, nonvascular neurological disease, musculoskeletal disease, hematologic disease, HIV or AIDS, anticoagulation, urogenital disease, and ophthalmologic disease), with 4 levels of severity for each condition. Information for the Index of Disease Severity was abstracted from dialysis unit records, hospital discharge summaries, medication lists, consultation notes, diagnostic imaging, and cardiac imaging reports. These data were collected at each dialysis unit, photocopied, and sent to New England Medical Center for abstraction and scoring. The Index of Physical Impairment is an observer-based assessment of 11 functional domains (circulation, respiration, neurologic function, mental function, urinary elimination, bowel elimination, feeding, ambulation, vision, hearing, and speech), each with 3 severity levels. The Index of Physical Impairment was completed by a local dialysis nurse who was familiar with the patients level of functioning, with input from a family member or caregiver if necessary. Two dialysis nurses with previous training and experience in using the Index of Coexistent Disease reviewed and scored all charts. The reliability of data abstraction and severity scoring was assessed by using a masked recoding of 45 charts. Interrater reliability, as assessed by the statistic, was excellent for Index of Disease Severity score ( = 0.93), maximum Index of Disease Severity score ( = 0.84), and maximum Index of Physical Impairment score ( = 1.0). Statistical Analysis We compared characteristics of patients undergoing peritoneal dialysis with those of patients undergoing hemodialysis by using analysis of variance for continuous variables and the Pearson chi-square test for categorical variables. The C-reactive protein level was log-transformed to reduce skewness of distribution. Patients were followed for death for up to 7 years. We used survival analysis to assess the presence, direction, strength, and independence of an association between dialysis technique and death. We used stratified Cox proportional hazards models to assess the risk for death among patients undergoing peritoneal dialysis versus those undergoing hemodialysis, independent of differences in demographic characteristics (age, sex, ethnicity, and employment status), clinical factors (smoking status, score on the Index of Coexistent Disease, diabetes status, history of cardiovascular disease, primary cause of renal failure, late referral to a nephrologist [<4 months from first evaluation by a nephrologist to initiation of dialysis], body mass index, and baseline residual urine output), and laboratory values (serum albumin level, hemoglobin level, calcium-phosphate product, total cholesterol level, C-reactive protein level, and creatinine concentration). We censored patients at transplantation or loss to follow-up. As the main analysis, we used intention-to-treat models based on the type of dialysis at baseline. Within the limitations of an observational study, this analysis was an attempt to replicate the intention-to-treat analysis in a clinical trial. If we could have adjusted for all of the factors that determine the choice of initial treatment technique, our results would mirror those of a randomized, controlled trial. We believe that this is the most important matter from the clinical point of view, because the real therapeutic choice for the clinician and the patient occurs primarily at the time of initiation of dialysis, whereas future switches may be motivated by treatment failures over which clinicians have little control. For the intention-to-treat models, we used multivariate Cox models that included all covariates, as well as models that incorporated dialysis technique and a technique propensity score. The propensity score, an established method used to address selection bias due to observed factors, is the estimated probability of being treated initially with peritoneal dialysis rather than hemodialysis. This propensity score, which

Pregnancy as state of physiologic absorptive hypercalciuria

An increase in circulating, 1,25-dihydroxyvitamin D level and net intestinal calcium absorption have been previously demonstrated in pregnant women and have been widely regarded as compensatory mechanisms whereby fetal mineral demands are satisfied. The alternate possibility, that these adjustments might anticipate such demands, has not previously been considered. To examine the effects of pregnancy on the intestinal absorption and renal excretion of calcium, oral calcium tolerance tests were performed and urinary calcium excretion was measured in 16 healthy women receiving a moderate calcium intake during and after pregnancy. Circulating 1,25-dihydroxyvitamin D levels and indexes of parathyroid function were also measured. As expected, 1,25-dihydroxyvitamin D levels were significantly (p less than 0.05) elevated throughout pregnancy (94 +/- 11, 118 +/- 9, and 117 +/- 11 pg/ml in the first, second, and third trimesters, respectively, versus 51 +/- 5 pg/ml after delivery). Twenty-four-hour calcium excretion also increased sharply (247 +/- 54, 316 +/- 42, 300 +/- 61 mg versus 91 +/- 18 mg), often to the point of hypercalciuria. Calcium tolerance test results included significant increases in the calciuric and calcemic responses during each trimester, whereas fasting calcium excretion and parathyroid function remained normal. These findings portray normal pregnancy as a state of physiologic absorptive hypercalciuria and call into question the widespread practice of supplementing calcium intake in otherwise well-nourished women during pregnancy.

Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy.

BACKGROUND Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD. METHODS To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen. RESULTS Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy. CONCLUSIONS Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.

Fungal peritonitis in a large chronic peritoneal dialysis population: a report of 55 episodes

Fungal peritonitis (FP) is a rare but serious complication of chronic peritoneal dialysis (CPD) therapy and is associated with high morbidity and CPD drop-out. Risk factors and management of FP remain controversial. We reviewed our experience with FP in an attempt to identify risk factors and to examine outcome in relation to treatment strategies. Between March 1984 and August 1994, 704 patients were maintained on CPD therapy in our unit. A total of 1,712 episodes of peritonitis were identified among these patients. Fungal peritonitis accounted for 55 (3.2%) of these episodes. The patients on CPD therapy who developed FP were similar to those who did not develop FP with regard to age, gender, underlying etiology for end-stage renal disease, and comorbid disease. Prior antibiotic use was noted in 87.3% of episodes of FP. The peritonitis rate in the patients who developed FP was one episode every 5.1 months compared with one episode every 9.9 patient-months in the CPD patients who did not develop this infection. Candida sp caused 74.5% of the episodes of FP. All patients were treated with antifungal drugs. In 85.5% of infections the Tenckhoff catheter was removed within 1 week of the diagnosis of FP; 31.9% of the patients who had the Tenckhoff catheter removed did not have the catheter replaced because of death or transfer to hemodialysis. In the patients who developed FP, 68.1% had the Tenckhoff catheter replaced; of these patients, 90.6% and 59.4% were on CPD therapy 1 and 6 months after catheter replacement, respectively. We conclude that risk factors identified in our population include peritonitis rate and prior antibiotic use. Fungal peritonitis is rare in our CPD population, and although it leads to significant CPD drop-out, it can be managed in many patients with antifungal therapy, early catheter removal, and temporary hemodialysis. Of the catheters replaced between 2 and 8 weeks after the diagnosis of FP, 91% functioned successfully, allowing continuation of CPD.

Identification and treatment of depression in a cohort of patients maintained on chronic peritoneal dialysis.

Depression is the most commonly encountered psychological problem in patients with end-stage renal disease (ESRD). Depression has recently been shown to significantly impact on the morbidity and mortality of patients undergoing therapy for ESRD. The present study was designed as a pilot study to evaluate the feasibility of screening a large cohort of patients maintained on chronic peritoneal dialysis (CPD) for depression and then pharmacologically treating those patients assessed to have clinical depression. One hundred thirty-six patients maintained on CPD in our CPD unit were screened for depression using the Beck Depression Inventory (BDI), a self-administered questionnaire. Patients with scores of 11 or greater were referred to a trained psychiatric interviewer for further evaluation to confirm the diagnosis of clinical depression and determine whether the patient was a candidate for antidepressant medication. Sixty-seven patients had BDI scores of 11 or greater, and 60 of these patients were asked to participate in further evaluation and possible therapy. Only 27 patients agreed to further study and were evaluated by a trained psychiatric interviewer for clinical depression. Twenty-three of these patients were assessed to have clinical depression, and 22 patients were eligible for antidepressant medication based on their scores on the Hamilton Depression Scale and psychiatric interview. Eleven patients completed a 12-week course of therapy with antidepressant medication, and their BDI scores decreased from a mean of 17.1 +/- 6.9 (SD) to a mean of 8.6 +/- 3.2. Seven patients were treated with sertraline, 2 patients with bupropion, and 2 patients with nefazodone. It is concluded that (1) depression is commonly present in patients maintained on CPD, (2) the BDI is a useful tool to use to screen for clinical depression, and (3) clinical depression is treatable with medication in this patient population.

Differing outcomes of gram-positive and gram-negative peritonitis

Peritonitis remains the leading cause of patient dropout from continuous peritoneal dialysis (CPD) therapy. Few studies have compared patient morbidity, mortality, and outcome for patients undergoing CPD who develop gram-positive and gram-negative peritonitis. We retrospectively reviewed the charts of patients who developed either gram-positive or gram-negative peritonitis between January 1, 1993, and December 31, 1995. Three hundred seventy-five patients who developed 415 episodes of gram-positive and gram-negative peritonitis were maintained on CPD therapy during this time period. There was no difference in age, race, and sex between patients who developed gram-positive or gram-negative peritonitis. More patients with diabetes developed gram-negative peritonitis than gram-positive peritonitis (53% v 40%, respectively; P < 0.05). Coagulase-negative staphylococcal species accounted for 47% of all gram-positive episodes, whereas Klebsiella organisms, Escherichia coli, and Enterobacter organisms accounted for 63% of all gram-negative episodes. Significantly more patients who developed gram-positive peritonitis continued CPD therapy 2 weeks and 6 months after the onset of peritonitis than patients who developed gram-negative peritonitis (97% v 73%; P < 0.05 at 2 weeks and 81% v 58% at 6 months; P < 0.05, respectively). Nine percent of the patients who developed gram-positive peritonitis died within 6 months after the onset of peritonitis, whereas 21% of the patients who developed gram-negative peritonitis died (P < 0.05). Patients who developed gram-negative peritonitis were significantly more likely to require hospitalization than patients who developed gram-positive peritonitis (74% v 24%; P < 0.001). More patients with gram-negative peritonitis required peritoneal catheter removal than patients with gram-positive peritonitis (18% v 4%; P < 0.001). Thirty-two percent of the patients who developed gram-positive peritonitis re-developed an episode of peritonitis with the same organism compared with only 9% of the patients who developed gram-negative peritonitis. Furthermore, peritonitis recurrence with the same organism within 6 months after the initial episode was noted in 60% of the patients with peritonitis caused by Staphylococcus aureus compared with 24% of patients with peritonitis caused by other gram-positive organisms (P < 0.05). We conclude that the outcomes of gram-positive and gram-negative peritonitis are different. When rates of peritonitis are used to predict outcome, it appears that gram-positive and gram-negative peritonitis rates need to be examined separately.

Effect of frequent hemodialysis on residual kidney function

Frequent hemodialysis can alter volume status, blood pressure and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to 6 compared to 3 times per week hemodialysis on follow up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 l/d, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared to controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared to 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 l/d, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined.Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined.

POSTTRANSPLANT BONE DISEASE: EVIDENCE FOR A HIGH BONE RESORPTION STATE

Loss of bone is a significant problem after renal transplant. Although bone loss in the first post transplant year has been well documented, conflicting data exist concerning bone loss after this time.It is equally unclear whether bone loss in long-term renal transplant recipients correlates with bone turnover as it does in postmenapausal osteoporosis. To examine these issues, we conducted a cross-sectional study to define the prevalence of osteoporosis in long-term (>1 year) renal transplant recipients with preserved renal function (mean creatinine clearance 73±23 ml/min). Bone mineral density (BMD) was measured at the hip, spine and wrist by DEXA in 69 patients. Markers for bone formation (serum osteocalcin) and bone resorption [urinary levels of pyridinoline (PYD) and deoxypyridinoline (DPD)] were also measured as well as parameters of calcium metabolism. Correlations were made between these parameters and BMD at the various sites. The mean age of the patients was 45±11 years. Eighty eight percent of patients were on cyclosporine (12% on tacrolimus) and all but 2 were on prednisone [mean dose 9±2 mg/day)]. Osteoporosis (BMD more than 2.5 SD below peak adult BMD) at the spine or hip was diagnosed in 44% of patients and osteopenia was present in an additional 44%. Elevated levels of intact parathyroid hormone (i PTH) were observed in 81% of patients. Elevated urinary levels of PYD or DPD were present in 73% of patients and 38% had elevated serum levels of osteocalcin. Levels of calcium, and of 25(OH) and 1,25(OH)2 vitamin D were normal. In a stepwise multiple regression model that included osteocalcin, PYD, DPD, intact PTH, age, years posttransplant, duration of dialysis, cumulative prednisone dose, smoking, and diabetes: urinary PYD was the strongest predictor of bone mass. These results demonstrate that osteoporosis is common in long-term renal transplant recipients. The data also suggest that elevated rates of bone resorption contribute importantly to this process.