Early Stages Of Renal Disease Research Articles

Left Ventricular Hypertrophy in Nondiabetic Predialysis CKD

Although left ventricular hypertrophy (LVH) is a strong predictor of mortality in patients with end-stage renal disease, few studies are available before the start of dialysis treatment. The purpose of this study is to evaluate the prevalence and clinical correlates of LVH in nondiabetic patients with chronic kidney disease (CKD) not yet undergoing renal replacement therapy. We investigated 244 nondiabetic patients with CKD; 57 patients (42 men; age, 20 to 78 years) had stages 1 to 2 CKD and 187 patients (122 men; age, 18 to 77 years) had stages 3 to 5 CKD. Fifty-two normotensive healthy subjects served as controls. Each patient had blood pressure (BP) measured by means of 24-hour ambulatory BP monitoring and left ventricular mass index (LVMi) assessed by means of M-mode echocardiography. Creatinine clearance was estimated by means of the Cockcroft-Gault formula, and hemoglobin, serum lipid, and intact parathyroid hormone concentrations and daily urinary protein excretion were assessed by using routine methods. In the overall group, prevalences of arterial hypertension and LVH were 66% and 74%, respectively. LVMi was 160 +/- 50 g/m2 body surface area and associated directly with age (P = 0.0013), duration of arterial hypertension (P = 0.0075), 24-hour systolic BP (P = 0.0113), pulse pressure (P = 0.0003), daytime (P = 0.0206) and nighttime systolic BP (P = 0.0059), and urinary protein excretion (P < 0.05) and inversely with creatinine clearance (P = 0.0103) and hemoglobin level (P = 0.0276). In patients with CKD stages 1 to 2 (LVH prevalence, 51%), age, duration of arterial hypertension, pulse pressure, and urinary protein excretion were significant predictors of LVMi (P < 0.00002) by using stepwise regression analysis, whereas in those with CKD stages 3 to 5 (LVH prevalence, 78%), pulse pressure emerged as the sole predictor of LVMi (P = 0.0011). The prevalence of LVH in nondiabetic predialysis patients with CKD is greater than previously reported, and there is evidence that LVH already is present in the early stages of renal disease. Arterial hypertension is associated with LVH in patients with CKD, and the strong relationship between elevated pulse pressure and LVH in those with more advanced CKD suggests that increased arterial stiffness might have a role for LVH well before the start of dialysis therapy.

Detrimental Effects of a High Fat Diet in Early Renal Injury Are Ameliorated by Fish Oil in Han:SPRD-cy Rats

Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory injury. We previously demonstrated that a high fat (HF) diet worsens early renal disease progression in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet) diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF compared with those fed LF diets had larger kidneys, more renal fibrosis and lower creatinine clearance (main effects of fat level). Rats fed MO rather than CO and SO diets had significantly lower kidney weights, kidney water content, cyst volumes and serum cholesterol and triglyceride concentrations (main effects of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO diets, but the least fibrosis was in rats fed SO diets. Analysis of simple effects (due to interactions between fat level and type) revealed that HF diets increased renal inflammation in rats fed CO diets, but reduced inflammation was present in those fed SO and MO diets; HF diets also increased compared with LF diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not the SO diet. These results confirm that high dietary fat worsens early disease progression in this model of renal disease, and further demonstrate that diets with oils containing (n-3) fatty acids ameliorate some of the detrimental effects of a high fat diet.

Atorvastatin and the dyslipidemia of early renal failure

Information about lipid abnormalities and the effect of lipid lowering therapy in the early stage of renal disease is limited, while preventive treatment in this stage might be much more beneficial. Lipid profiles and risk factors were assessed in 150 consecutive, non-diabetic patients. Preventive therapy consisted of cholesterol-reduced diet and atorvastatin 10 mg daily. Patients were considered at risk for cardiovascular disease if LDL-cholesterol was >2.6 mmol/l in the case of manifest cardiovascular disease ( n=28) or when they had manifest cardiovascular risk factors ( n=105) or if LDL was >3.5 mmol/l ( n=17). A total of 128 patients (85%) had increased LDL. In men <60 years and women <40 years, total cholesterol was higher than in the general population. Linear regression analysis showed a decreased creatinine clearance to be significantly associated with the lipid profile. For a 10 ml/min decrease of creatinine clearance, a 0.085 increase of the total cholesterol to HDL ratio was observed ( P=0.005). In similar analyses, proteinuria was strongly associated with cholesterol and triglycerides. An increase of 0.28 of the total cholesterol/HDL ratio was observed for each gram per 24 h proteinuria ( P<0.001). On atorvastatin 10 mg daily, 30 of 60 treated patients had achieved their target LDL value. On average, LDL-cholesterol was reduced by 39% and triglycerides by 18%. No patient had to interrupt their treatment because of adverse side-effects. In conclusion, the majority of patients had an elevated LDL and other lipid abnormalities. Short-term therapy with atorvastatin and a cholesterol lowering diet appears to be safe and effective. It is probably useful to determine the lipid profile in patients with renal failure already in an early phase and to start lipid lowering treatment as soon as abnormalities are found.

Does magnesium dysbalance participate in the development of insulin resistance in early stages of renal disease?

We investigated the potential role of magnesium (Mg) dysbalance in the pathogenesis of insulin resistance (IR) in patients with mildly-to-moderately decreased renal function (creatinine: 142.8±11.0 mmol/l). The data were compared to those of 8 age- and sex-matched healthy controls (CTRL). The standard oral glucose tolerance test (oGTT) was performed in 61 patients. Twenty-two patients were classified as IR according to their values on fasting and after-load immunoreactive insulin concentrations. Serum and total erythrocyte Mg (tErMg) (atomic absorption spectro-photometry) and free erythrocyte Mg (fErMg) concentrations (31P NMR spectroscopy) were determined prior to and two hours after the glucose load. Ten out of 39 insulin-sensitive (IS) patients, but only one out of 22 insulin-resistant (IR) patients, had a low basal fErMg concentration (&lt;162.2 mmol/l, c2, p&lt;0.01). IR patients had higher serum Mg, total erythrocyte Mg and bound erythrocyte Mg (bErMg) concentrations (both before and after glucose load) when compared with the IS group. Both groups responded to the glucose load with a significant decrease in serum Mg concentration (within the normal range), while the IR group also exhibited a decline in tErMg and bErMg. The mean sum of insulin needed to metabolize the same glucose load correlated positively with tErMg (r=0.545, p&lt;0.01) and bErMg (r=0.560, p&lt;0.01) in the IR patients. It is concluded that, at an early stage of renal dysfunction, IR is not associated with the decline in free erythrocyte Mg concentration, but the magnesium handling in red blood cells is altered.

Protein Restriction in Renal Disease

Abstract Early stages of renal disease alter the metabolism of nutrients and their end products. In addition, food intake is limited because of gastrointestinal distress, depression, superimposed illness, and restrictive diets. Treatment of chronic renal failure (CRF) is multifactorial and should focus on dealing with uremia, muscle wasting, metabolic acidosis, blood pressure, and adequate energy intake. Protein intake is a modulator of renal function. Conventional protein restriction of about 0.6 g/kg body weight/day has been recommended in patients with moderate CRF to reduce signs and symptoms of uremia and to delay the progression of renal disease. Like healthy individuals, CRF patients seem able to activate normal compensatory responses to dietary protein restriction in order to maintain lean body mass and nutritional status. Low‐protein diets do not seem to worsen survival during dialysis. In contrast, high dietary protein intake results in metabolic acidosis and anorexia. Anorexia, in turn, limits energy intake and reduces the efficiency of protein utilization. Thus, a low‐protein diet that approaches the minimal requirement for reducing anorexia while preventing malnutrition is a clinical challenge for the treatment of CRF patients not yet on dialysis. To successfully achieve the goals of protein‐restricted regimens, intensive nutritional counseling (at no less than 1‐ to 3‐month intervals) should be a routine component of care in this patient population.

Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria.

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A, macroalbuminuric diabetic patients had higher serum leptin levels than the normoalbuminuric diabetics (11.90 +/- 2.98 v 4.13 +/- 0.92 ng/mL, P < .002) and control subjects (4.78 +/- 1.37 ng/mL, P < .006). In group B, microalbuminuric diabetics had higher serum leptin levels than the normoalbuminuric diabetics (21.16 +/- 5.80 v8.74 +/- 1.89 ng/mL, P < .04) and control subjects (10.06 + 3.00 ng/mL, P < .06). In both groups A and B, creatinine clearance was inversely correlated with the serum leptin level after adjusting for body fat. In conclusion, serum leptin levels are elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is already impaired in the early stages of renal disease.

Early stages of renal disease

Early stages of renal disease

Early Stages of Renal Disease.

Early Stages of Renal Disease.

Histological changes in parathyroid glands in subclinical and clinical renal disease. An autopsy investigation.

In an autopsy material of patients with varying degrees of renal impairment, the parathyroid glands were examined regarding glandular and parenchymal cell weights and cellular types and arrangement. The findings were related to the different stages of renal disease. The study comprised 69 cases--29 females and 40 males. Their mean age was 74 years (range 33-98 years). There was a positive relation between serum creatinine level and total parathyroid parenchymal cell weight (r=0.37, p less than 0.01) and an inverse correlation between kidney weights and parathyroid parenchymal cell weight (r=-0.24, p less than 0.05). The patients with the most advanced renal impairment had significantly higher mean total glandular and mean total parenchymal weights than those with less pronounced renal disease. Nodular arrangement and an increased number of oxyphil and transitional oxyphil cells were noted in cases with advanced histological kidney changes but normal serum creatinine levels. This nodularity as well as the frequency of oxyphil cells increased in parallel with deterioration of renal function. The two most important factors that influenced the proportion of oxyphil cells were the parenchymal cell weights and the age of the patient. It is concluded that signs of stimulation of the parathyroids are present already in early stages of renal disease, in some cases before renal dysfunction is clinically manifested.

Effect of various protein diets on growth, renal function, and survival of uremic rats

The effects on growth, renal function, and survival of three isocaloric diets of various protein content (14, 27, and 37 g/100 g in diets I, II, and III, respectively) were compared in uremic rats and in controls. Diet I provided the minimal requirements in all amino acids for gorwing rats. In controls fed ad lib, weight and length gain were better with high protein diets, whereas they were inversely related to the diet protein content in uremic rats. The higher the protein intake, the higher the progressive elevation of BUN and serum creatinine and the mortality rate. Because proteins were supplied by fish flour, their increase was associated with increased mineral content, and the conclusions are restricted to the use of natural proteins: a moderately restricted protein diet securing only the minimal requirements had a beneficial effect on growth and survival of rats with reduced kidney mass. Avoiding any excess in proteins from the early stage of renal disease is suggested.

The pathogenesis of secondary hyperparathyroidism of renal failure. Is there a controversy?

Hyperplasia of the parathyroid glands and elevated blood levels of parathyroid hormone (PTH) are almost always present in patients with chronic renal failure. 1-6 The evidence of this secondary hyperparathyroidism is found even with mild renal insufficiency. 5 Therefore, the mechanism(s) underlying this abnormality must be operative in the early stages of renal disease. MECHANISMS OF HYPOCALCEMIA OF RENAL FAILURE All investigators agree that the stimulus for the hyperplasia of parathyroid glands in these patients is hypocalcemia. A great deal of effort has been devoted to investigate the mechanism(s) of the hypocalcemia of renal failure. At present, two postulates have been advanced. These include phosphate retention 7,8 and skeletal resistance to the calcemic action of PTH. 9-14 The proponents of these two notions have provided evidence supporting their concepts. The vigor with which this has been done perpetuated the impression that these two theories are mutually exclusive and, as such,

The Kidney Structure and Function in Disease.

This monograph is the first of a series on major organ systems of the body—attempting to integrate structural abnormalities with functional change. By using an interdisciplinary approach, an outgrowth of the authors' experience in presenting the Georgetown University Medical Center Renal Biopsy Conference, several innovative features make the monograph attractive. The book reads easily and illustrations are placed for reader convenience. The material is not repetitive. The authors are succinct and avoid prolonged discussion of controversial, unsettled matters. The book demonstrates the value of the interdisciplinary approach (pathology and internal medicine) particularly in the early stages of renal disease. The presentation of material combining the clinical setting, functional change, and the pathological aspects of renal disease makes for clarity and greatly reduces many of the nomenclature problems which have beset the field. The monograph is divided into 11 chapters which cover most clinical problems encountered in medical practice. It is

The concentrating ability of the renal system in health and in diseased states

A test of general renal function based on the measurement of urine osmolality has been applied to a group of normals, a group of control patients, and a series of patients suffering from renal disease of varying severity. The results obtained have been compared with the Van Slyke urea clearance tests carried out at the same time. In normal subjects and in the early stages of renal disease the two tests give reasonably similar results. In the advanced cases of renal disease, there is a marked discrepancy between the two assessments of renal function.