Pilot Randomized Controlled Trial of a Standard Versus a Modified Low-Phosphorus Diet in Hemodialysis Patients.

INTRODUCTION: The standard low-phosphorus diet restricts pulses, nuts, and whole grains and other high phosphorus foods to control hyperphosphatemia. We conducted a randomized controlled trial to evaluate the effectiveness, safety, and tolerability of the modified diet, which introduced some pulses and nuts, increased the use of whole grains, increased focus on the avoidance of phosphate additives, and introduced the prescription of low-biological-value protein such as bread. METHODS: We conducted a multicenter, pragmatic, parallel-arm, open-label, randomized controlled trial of modified versus standard diet in 74 adults on hemodialysis with hyperphosphatemia over 1 month. Biochemistry was assessed using monthly laboratory tests. Dietary intake was assessed using a 2-day record of weighed intake of food, and tolerability was assessed using a patient questionnaire. RESULTS: There was no significant difference in the change in serum phosphate between the standard and modified diets. Although total dietary phosphorus intake was similar, phytate-bound phosphorus, found in pulses, nuts, and whole grains, was significantly higher in the modified diet (P < 0.001). Dietary fiber intake was also significantly higher (P < 0.003), as was the percentage of patients reporting an increase in bowel movements while following the modified diet (P = 0.008). There was no significant difference in the change in serum potassium or in reported protein intake between the 2 diets. Both diets were similarly well tolerated. CONCLUSION: The modified low phosphorus diet was well tolerated and was associated with similar phosphate and potassium control but with a wider food choice and greater fiber intake than the standard diet.

Increased Weight Gain During the Long Interdialytic Period Is Associated with Minor Effects on Blood Pressure Control in Clinically Stable In-Centre Haemodialysis Patients.

BACKGROUND/AIMS: Three-day-a-week chronic haemodialysis (cHD) involves 1 long (72 h) and 2 short (48 h) inter-dialytic periods (IDPs). We aimed to determine whether BP control following the long IDP is inferior to the short IDPs. METHODS: All pre- and post-dialysis BP and weight measurements over a 4-week period were retrospectively analyzed among 135 clinically stable cHD patients at 2 academic centres with comparisons between measurements recorded following short and long IDPs. Subsequently, 23 clinically stable cHD patients underwent 24-h ambulatory blood pressure monitoring (ABPM) during the final day/night cycle of the long IDP and 1 short IDP within the same week. RESULTS: In combined and separate analyses of the 2 retrospective cohorts, pre-dialysis BP parameters were not different following long and short IDPs despite greater inter-dialytic weight gain (IDWG) during the long IDP. Subgroup analyses of the total cohort showed no evidence for inferior BP control during the long IDP among those with high %IDWG. In the ABPM study, nocturnal hypertension and loss of nocturnal dipping were frequent. Furthermore, daytime systolic blood pressure (SBP) and pulse pressure were modestly higher during the last day/night cycle of the long compared with short IDP. CONCLUSION: In stable cHD patients, the greater IDWG that occurred during the long IDP was not associated with overtly inferior BP control as reflected in pre-dialysis BP measurements. However, modestly higher daytime SBP was evident towards the end of the long IDP by 24 h ABPM. Thus, while fluid gain has well-documented associations with hypertension and adverse cardiovascular outcomes, the excess IDWG that occurs during the long IDP exerts relatively minor effects on BP control in patients on well-established dialysis regimens that are better identified by ambulatory monitoring.

Lipid mediators of inflammation in obesity-related glomerulopathy.

The interplay between chronic kidney disease (CKD) and obesity represents the convergence of two of the most common contemporary clinical issues, and is of particular interest and significance in the context of the burden presented by each at present, and the dismal projections associated with both of these conditions for the future. That obesity leads to CKD through its association with other risks, such as hypertension, type 2 diabetes mellitus and atherosclerosis, is well established; however, it is likely that obesity itself is an independent risk factor for the development of CKD. The aetiology of this obesity-related glomerulopathy (ORG) is not clear, but it appears to be strongly influenced by chronic inflammation, manifest as a disturbance of the balance between pro-inflammatory and pro-resolving lipid mediators, adipokines and mononuclear cells. This review examines the association between obesity and CKD, the role of inflammation therein, and the potential for pro-resolving lipid mediators to restore homoeostasis and offer therapeutic potential in ORG.

Allelic depletion of grem1 attenuates diabetic kidney disease.

OBJECTIVE: Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy. RESEARCH DESIGN AND METHODS: Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes. RESULTS: A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1(+/-) mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1(+/-) and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1(+/-) mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1. CONCLUSIONS: These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.

Subjective and objective physical limitations in high-functioning renal dialysis patients.

BACKGROUND: The utility of subjective measures of physical function as discriminative, evaluative and predictive tools in patients with ESRD is accepted, but objective performance tests also provide valuable information on patient status. The aims of this study were to determine what objective physical limitations exist in a select group of dialysis patients, designated as 'high-functioning' on the basis that they had low comorbidity and subjectively perceived themselves to function well, and to examine relationships between the objective and subjective measures. METHODS: Twelve patients (male, 7; female, 5) aged 18-55 years, with scores of > or = 75 points in the Short Form-36 Physical Function scale (PF) and low comorbidity (Charlson score < or = 2) were recruited for comparison with age and sex-matched sedentary controls. Objective performance measures included vibration perception threshold (VPT), peak quadriceps isokinetic and isometric muscle torque, time to reach peak isometric torque, balance (body sway with eyes open and closed), temporal gait parameters and the sit to stand test (STST). RESULTS: Dialysis patients demonstrated significant deficits by comparison with controls in subjective PF score (P < 0.001), VPT (P < 0.01), quadriceps isometric and isokinetic torque (P < 0.05, P < 0.005), body sway with eyes open (P < 0.01) and closed (P < 0.05), self selected (P < 0.005) and maximum (P < 0.01) walk speed, duration of gait cycle (P < 0.05) and STST (P < 0.001). There was significant agreement between the subjective PF score and VTP (P < 0.01), isokinetic torque (P < 0.05), body sway with eyes open (P < 0.05) and closed (P < 0.05), self-selected walk speed (P < 0.01) and STST (P < 0.01). CONCLUSIONS: Subtle but significant deficits in subjective and objective physical function existed even in this select group of dialysis patients. These findings define in more detail the underlying neuromuscular impairments and support the early implementation of active targeted rehabilitation programmes. The subjective and objective measures used here offer a useful panel of tests for clinical use in high-functioning dialysis patients.