Gender and age differences in plasma carnitine, muscle strength, and exercise tolerance in haemodialysis patients.

BACKGROUND: Haemodialysis patients have impaired exercise tolerance that may be related to impaired carnitine availability and/or alterations in carnitine metabolism. As carnitine metabolism is sex- and age-related, we examined plasma free and esterified carnitine concentrations, muscle strength, and estimated exercise tolerance in female (n=51) and male (n=63) patients of different ages (18-86 years). METHODS: Concentrations of free carnitine and acetylcarnitine were determined in the plasma of patients. Isometric handgrip strength was measured using a dynamometer while exercise tolerance was predicted from scores for self-reported walking distance on the level and on an incline. RESULTS: Plasma total carnitine concentration in the females was significantly lower than that of males (35.4+/-1.3 and 42.4+/-1.4 micro mol/l, respectively, P<0.01). This was almost entirely due to the lower plasma free carnitine concentration of females when compared with the males (20.6+/-0.9 and 26.3+/-1.1 micro mol/l, respectively, P<0.05). Furthermore, plasma free carnitine concentrations were negatively correlated with age in females (r=-0.45, P<0.001) even when the linear effects of haemoglobin, albumin, body weight, time on dialysis, and muscle strength were removed from the regression analysis (partial correlation coefficient; pcc=-0.43, P=0.018), but not in the males (r=0.03, P>0.05). Isometric handgrip strength and estimated exercise tolerance on the level were lower in females than males (138.9+/-10.9 and 259.0+/-15.2 N, P<0.001; and 3.5+/-0.2 and 4.3+/-0.2, P<0.05, respectively). Isometric handgrip strength and estimated exercise tolerance (walking distance on the level and on an incline) were positively correlated with plasma free carnitine concentrations in females, but not in the males. CONCLUSIONS: There was a strong relationship between plasma free carnitine concentrations and age in female patients, but not in males. It is unlikely that the reduction in plasma free carnitine in females was a direct causative factor in their reduced exercise tolerance, but probably reflects greater muscle de-conditioning/atrophy with age in female patients.

Renal function in sickle cell patients over 40 years old - abstract

There are few data on renal function in older adults with homozygous sickle cell disease although renal failure is a common cause of death. Twelve males and 13 females between 40 and 64 years old were studied when free of acute complications of their disease. Eight had renal insufficiency as defined by creatinine clearance (Ccr) less than 100 ml/min/1.73m2. When compared with the 17 others they showed no significant difference in sex, IVP abnormality, history of sickle cell crisis, or leg ulceration. Although the greater mean age of the patients with renal insufficiency was not statistically significant (52.1 vs 46.9 years, p>0.05) the whole group showed a negative correlation between Ccr and age (r= -0.55, p<0.01). Anaemia was more marked in those with renal insufficiency (mean Hb 5.9 vs 8.4 g/dl, p<0.001) and there was a strong linear correlation of Hb with Ccr (r= 0.76, P<0.001). Proteinuria greater than 100 mg/day was significantly more common in those with renal insufficiency (p<0.01) but no patient had either gross proteinuria or a history of nephrotic syndrome. This group probably contained no patients with immune complex sickle cell glomerulonephropathy since this quickly progressive disease presents most commonly with severe nephrotic syndrome in the third and fourth decade. Older patients probably develop renal insufficiency because of the destructive effects of the sickling process on the renal microvascualture. Worsening anaemia is a sensitive early indicator of failing renal function, perhaps because the bone marrow activity is critically dependent upon erythropoietin production by the kidney (AU)

Proteinuria and leg ulcers in homozygous sickle cell disease

In a survey of 407 patients with homozygous sickle cell disease in Jamaica, 50 had proteinuria of "+" or more on dipstick testing and 231 had had leg ulcers. Both proteinuria and ulcers began to occur mainly in the second decade of life and their prevalence increased with age thereafter. When allowance was made for this there was no significant association between the two, and it is therefore likely that they result from independent effects of the haemoglobinopathy on the kidneys and skin. Though asymptomatic and relatively common, proteinuria in sickle cell disease is not a benign finding since it is associated with renal failure in patients over 40 years old (AU)

Impaired peritoneal fluid drainage in nephrogenic ascites

In three chronic hemodialysis patients nephrogenic ascites and in four patients with ascites of other causes the rate of transfer of fluid from peritoneal cavity to plasma was measured by a radio-labelled albumin method. Ascitic fluid removal rate was lowered in the patients with nephrogenic ascites (median 14, range 10 to 21ml/hr) than in those with normal renal function (median 45, range 10 to 73 ml/hr). These results suggest that lymphatic drainage of the peritoneum is impaired in nephrogenic ascites and that this may contributed to the development of the condition and to the propensity of fluid overloaded dialysis patients to develop ascites. A retained substance or one liberated from abnormal kidneys nay be responsible for reversible for reversible depression of lymphatic flow in uremia. (AU)

Renal function in patients over 40 with homozygous sickle-cell disease

Renal function was examined in 25 patients aged 40-64 with homozygous sickle cell disease. Investigations included intravenous urography and measurement of blood urea and creatinine concentrations and creatinine and protein excretion in 24-hr collections of urine. Serum creatinine concentrations did not differ significantly from those of 25 other patients with SS disease aged 18-39 years, but sreum urea concentrations were significantly higher (p<0.001). Intravenos urography showed loss of caliceal cupping (nine patients), irregular renal outline (five), and cystic extension from the calix (one). Six patients had creatinine clearances below the fifth percentile for age and sex. Proteinuria was more common in these patients, and haemoglobin concentrations were much lower than in the 19 patients without renal insufficiency (mean 5.6 vs 8.2 g/dl; p<0.001). Haemoglobin concentration was strongly correlated with creatinine clearance (r=0.70), particularly with clearances below 100 ml/min/1.73 m2 (r=0.96; p,0.001). A possible mechanism of renal insufficiency in SS disease is cortical scarring, which is asymptomatic, not associated with hypertension, and accompanied by only minor proteinuria. A falling haemoglobin concentration is a sensitive and early indicator of renal impairment in SS disease (AU)

Glomerular function and hyperuricaemia in sickle cell disease

Renal insufficiency is common in adults with homozygous sickle cell disease, and the contribution of glomerular failure to the hyperuricaemia which is often a feature of the disease has therefore been investigated. In a study of 64 patients between the ages of 15 to 66, serum urate concentration was dependent on renal urate clearance and also on creatinine clearance. The relation between serum urate and creatinine clearance was abnormal in patients with sickle cell disease and it is suggested that this might be caused by high single nephron glomerular filtration rates. Both the amount of urate excreted per millilitre of glomerular filtrate and the fractional excretion of urate increased with falling creatinine clearance, suggesting that the ability to increase tubular urate secretion was preserved. Patients with extensive tubular disease as shown by tubular proteinuria had serum urate concentrations which were not significantly different from those of age and sex matched non-proteinuric patients. Evidence that renal tubular disease interferes with urate secretion and causes hyperuicaemia in patients with sickle cell disease needs to be reinterpreted in the light of these findings.(AU)

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis - abstract

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine 1200 umol/1 and above and Group II comprised patients with serum creatinine 600 umol/1 and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) compared to Group I (Kt/V, 1.59; p <0.01). The mean duration of CAPD dialysis was significantly longer in Group I (3.12 years) compared to Group II (1.32 years; p <0.01). Also, the mean total creatinine clearance for Group II was significantly higher than for Group I (p <0.001). There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p <0.001); Kt/V and normalized protein catabolic rate (NPCR, r=0.6; p <0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and NAMC. Group II patients had a significantly better residual renal clearance (p <0.0001). Pruritus was a troublesome feature in Group I, but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer need to be done on these patients (AU)

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 umol/l and Group II comprised patients with serum creatinine concentration of 600 umol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years); (p < 0.01) patients, and the mean total creatinine clearance of Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer are in progress.(AU)

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom Hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89 percent being less than 60 years of age compared to 40 percent at NCH (p<0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI than at NCH but the numbers were small (p<0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p<0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76 percent v 19 percent on haemodialysis). At UHWI, CAPD was not available and 45 percent of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available. (AU)

Proteinuria and glomerular disease in Jamaica

Clinical, laboratory and renal biopsy data on 50 adult patients investigated in Jamaica because of proteinuria of more than 1 g/day were reviewed. Primary glomerular disease was present in 23 cases and the most common histological pattern was mesangial proliferation. Proteinuria was part of a systemic disease in 27 patients of whom 19 had systemic lupus erythematosus (SLE). Urinary protein excretion was less in patients with systemic diseases than in those with primary glomerulonephritis, but hypoalbuminemia, renal function and presence of edema were not helpful in distinguishing types and causes of renal disease. By comparison with other countries SLE and mesangial proliferative glomerulonephritis are common causes of proteinuria and nephrotic syndrome in Jamaica whereas idiopathic membranous glomerulonephropathy appears to be rare (AU)

Emphysematous pyelitis and papillary necrosis

We report the case of a 30-year-old diabetic woman who developed a urinary tract infection with the rare complications of emphysematous pyelitis and papillary necrosis. Both these complications are commoner in diabetics than in non-diabetics and emphysematous pyelitis is associated with a particularly poor prognosis, necessitating urgent surgery if antibiotic treatment fails. Papillary necrosis may cause obstruction acutely which may further magnify the problem. Long-term antibiotic therapy is recommended in view of the likelihood and danger of a recurrent urinary tract infection. (AU)

Renal pathology in adults over 40 with sickle-cell disease

In a retrospective study of hospital necropsies, we examined the kidneys of 21 patients with homozygous sickle-cell disease who died at the age of 40 or over. Renal failure had caused or contributed to death in ten cases. All kidneys showed changes of papillary damage to a variable extent. In three cases, there was mild cortical irregularity, and in thirteen, there was moderate to severe cortical irregularity, including scarring in some with obvious loss of functioning tissue. Light microscopic examination revealed hypertrophic glomeruli with increased cellularity, lobulation and capillary basement membrane splitting. Glomeruloscelerosis was common, and patchy deposists of fabrin were present in glomerular capillaries in four cases. Though factors contributing to these changes could include papillary necrosis and immune-complex glomerulonephritis, we suggest that sclerosis consequent upon longstanding hyperfiltration may be more important. Glomerular filtration rate is abnormally high in children with sickle-cell disease but in later childhood renal insufficiency, proteinuria and eventually death from renal failure become common (AU)

Plasma haemoglobin and complement activation in sickle cell disease

The role of haemolysis in producing deficient complement function in homozygous sickle cell disease was studied by measuring indices of complement activation and of haemolysis in 30 asymptomatic patients. Plasma concentration of C3d (an index of increased C3 turnover) was elevated in 40 percent of patients and modest decreases in serum concentration of C3 and functionally (haemolytically) active factor B were found. There was a positive correlation between C3d and plasma haemoglobin concentration (r = 0.56, p less than 0.005). Reticulocyte count and foetal haemoglobin concentration also contributed to variation in C3d, though to a lesser extent than plasma haemoglobin. Intravascular haemolysis in sickle cell disease may produce activation of complement and thus cause partial depletion of functional factor B and C3. This may reduce the immune function of the alternative pathway. (AU)

Erythropoietin and renal function in sickle-cell disease

The relations between haemoglobin concentration and creatinine clearance, and the serum concentration of erythropoiesis-stimulating factor were assessed in 31 patients with homozygous sickle-cell disease. Haemoglobin concentrations fell significantly with decreasing creatinine clearance (r=0.58, p<0.001) and were positively correlated with the concentration of erythropoiesis-stimulating factor (r=0.65, P<0.001). These observations suggest that erythropoietin concentration is the factor limiting production of red cells in sickle-cell disease with renal insufficiency and have implications for treatment (AU)

Haemodynamic improvements after peritoneovenous shunting in nephrogenic ascites

A patient being treated by regular hemodyalisis for end-stage renal failure had nephrogenic ascites. Despite attempts at fluid removal by ultrafiltration, progressive hypotension and low cardiac output eventually reduced fistula flow so much that haemodylasis became almost impossible. The insertion of a peritoneovenus shunt resulted in reduction of ascites and 78 percent increase in cardiac output, with consequent correction of hypotension and improvement of fistula flow. Peritoneovenous shunting is a simple and beneficial form of treatment for nephrogenic ascites that does not respond to fluid removal by dialysis (Summary)

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom Hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89 percent being less than 60 years of age compared to 40 percent at NCH (p<0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI than at NCH but the numbers were small (p<0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p<0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76 percent v 19 percent on haemodialysis). At UHWI, CAPD was not available and 45 percent of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 umol/l and Group II comprised patients with serum creatinine concentration of 600 umol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years); (p < 0.01) patients, and the mean total creatinine clearance of Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-a-vis solute transfer are in progress.

Cytomegalovirus infection in renal transplantation

Three case reports of cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropositive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortalitiy. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection (AU)

Renal transplantation in Jamaica

In a ten-year period beginning in 1970, twenty-five cadaver renal transplants were performed in Jamaica. Kidneys were transplanted with only short ischaemia times, and early function was a feature in most cases. Patient and graft survival were comparable with results obtained in larger centres even though tissue typing was not used to match donors and recipients. This experience shows that transplantation is an effective and suitable form of therapy for chronic renal failure in developing countries. Increasing awareness by the medical profession of the benefits of renal transplantation may increase the supply of donor kidneys and enable more patients with end-stage renal failure to receive treatment (AU)

Membranous glomerulonephropathy with crescents in systemic lupus erythematosus

Over a 2-year period percutaneous renal biopsies were carried out on 23 patients with systematic lupus nephritis. When classified by immunofluorescence, and light and electron microscopy, 4 patients had mesangial disease, 1 had focal and segmental proliferation, 5 had diffuse proliferation and 5 had membranous changes. 3 biopsies were unclassified with end-stage changes and 5 showed an unusual combination of pure membranous changes in association with significant crescent formation. The outcome of the latter group of patients was uniformly poor. We think that this group represents a distinct histological entity with a poor prognosis (AU)