Course Of Renal Function Research Articles

Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease.

Autosomal-dominant polycystic kidney disease results in renal failure at a varying age from childhood to old age. We postulated that factors other than the culprit gene alone contribute to the course of progression of the renal failure. We studied 580 subjects with autosomal-dominant polycystic kidney disease and 194 unaffected family members. We calculated survival curves to end-stage renal failure or death and developed a linear model for testing the effects of single or multiple variables on the progression of renal failure as estimated from the reciprocal of serum creatinine. Fifty-two subjects died and 94 reached end-stage renal failure during the period of observation, yielding functional survivals of 71% at age 50 years, 53% at 58 years and 23% at 70 years. The following variables were independently associated with worse mean renal function at a given age (P value less than 0.01): the PKD1 gene, younger age at diagnosis, male gender, hypertension, increased left ventricular mass, hepatic cysts in women, three or more pregnancies, gross hematuria, urinary tract infections in men and renal size expressed as renal volume. The following were not associated significantly with the course of renal function: gender of affected parent, mitral valve prolapse, intracranial aneurysms, any pregnancy, hepatic cysts in men and urinary tract infections in women. The identification of unalterable maleficent factors such as the PKD1 gene and male gender permit more informed counseling while the identification of alterable factors such as hypertension, number of pregnancies and recurrent urinary tract infections provides the clinician with the opportunity to modify these factors and improve the management of patients with autosomal-dominant polycystic kidney disease.

Acetaminophen nephrotoxicity in male Wistar rats.

Acute acetaminophen (APAP) nephrotoxicity was studied in male Wistar rats 1 h after different APAP single doses (200, 500 and 1000 mg/kg body wt, i.p.). Significant impairments in glomerular filtration rate (GFR) and clearance of p-aminohippuric acid (ClPAH) were observed in a dose-dependent way, although tubular parameters measured, water and electrolyte fractional excretion, remained at control values, while the urine to plasma osmolality ratios (Uosm/Posm) were diminished in APAP-1000 rats (control = 2.93 +/- 0.20, APAP-1000 = 1.40 +/- 0.04). The time course of renal function was also studied in APAP-1000 mg/kg-treated animals; parallel impairments were observed in GFR, ClPAH and tubular functions. Maximal alteration was observed at 16 h and restorement began at 24 h post-injection. Glucose renal handling, either at low or at high tubular glucose loads, remained at control values. Thus, our data suggest that the early stage of acetaminophen nephrotoxicity might be due to renal hemodynamic changes which might induce an alteration in tubular function principally in distal structures of medullary tissue, as shown by the Uosm/Posm results. These effects occurred coupled with a diminution in hepatic glutathione (GSH) levels at every APAP dose and in renal GSH levels in APAP-1000 mg/kg-treated rats. Moreover, renal damage was observed both in the presence or absence of hepatic damage.

Unpredictability of Clinical Evaluation of Renal Function in Cirrhosis. Prospective Study

The natural course of renal function in patients with cirrhosis and ascites but without azotemia is unclear. Therefore, a prospective evaluation of 23 non-azotemic cirrhotic patients with ascites was carried out over a three-year interval. Assessment included evaluation of serum electrolyte values, liver function tests, plasma renin levels, and parathyroid hormone levels. Renal function was determined by measurement of clearances of water and solute excretion, and simultaneous clearances of para-amino hippurate, inulin, and creatinine. The initial mean glomerular filtration rate was 66 ml/minute, serum creatinine level was 1.1 mg/dl, and blood urea nitrogen value was 13 mg/dl. The glomerular filtration rate showed marked variability among patients. On the basis of initial glomerular filtration rate, the patients were divided into three groups. Group I consisted of patients with supranormal filtration rates (mean 183 ml/minute), Group II constituted patients with normal filtration rates (mean 92 ml/minute), and Group III comprised patients with severely impaired filtration rates (mean 32 ml/minute). The serum creatinine level was below 1.5 mg/dl in all three groups. Serial measurement of renal function was performed in 18 patients over a mean of 310 days (range four to 1,176 days). Eighty-six percent of patients studied from Groups I and II maintained a normal or supranormal glomerular filtration rate over one year. However, most patients in Group III showed a progressive decline in filtration rate, despite no change in serum creatinine value. Sixty-seven percent of Group III patients died over a mean of one year. The mean 24-hour solute excretion among Group III patients was only 263 mOsm per day, significantly less than the control value of 874 mOsm per day in other hospitalized non-cirrhotic patients. The serum creatinine level frequently failed to rise above normal even when the glomerular filtration rate was very low (less than 25 ml/minute), and creatinine clearance overestimated inulin clearance by a factor of two in Group III patients. However, the creatinine index was an aid in determining true glomerular filtration rate and may be a useful clinical test in the evaluation of renal insufficiency in cirrhotic patients with normal serum creatinine values. Many patients with cirrhosis and ascites will have a glomerular filtration rate of less than 60 ml/minute but a normal serum creatinine level. These patients may constitute a previously unrecognized large group.

Unpredictability of clinical evaluation of renal function in cirrhosis: Prospective study

The natural course of renal function in patients with cirrhosis and ascites but without azotemia is unclear. Therefore, a prospective evaluation of 23 non-azotemic cirrhotic patients with ascites was carried out over a three-year interval. Assessment included evaluation of serum electrolyte values, liver function tests, plasma renin levels, and parathyroid hormone levels. Renal function was determined by measurement of clearances of water and solute excretion, and simultaneous clearances of para-amino hippurate, inulin, and creatinine. The initial mean glomerular filtration rate was 66 mi/minute, serum creatinine level was 1.1 mg/dl, and blood urea nitrogen value was 13 mg/dl. The glomerular filtration rate showed marked variability among patients. On the basis of initial glomerular filtration rate, the patients were divided into three groups. Group I consisted of patients with supranormal filtration rates (mean 183 ml/minute), Group II constituted patients with normal filtration rates (mean 92 ml/minute), and Group III comprised patients with severely impaired filtration rates (mean 32 mi/minute). The serum creatinine level was below 1.5 mg/dl in all three groups. Serial measurement of renal function was performed in 18 patients over a mean of 310 days (range four to 1,176 days). Eighty-six percent of patients studied from Groups I and II maintained a normal or supranormal glomerular filtration rate over one year. However, most patients in Group III showed a progressive decline in filtration rate, despite no change in serum creatinine value. Sixty-seven percent of Group III patients died over a mean of one year. The mean 24-hour solute excretion among Group III patients was only 263 mOsm per day, significantly less than the control value of 874 mOsm per day in other hospitalized non-cirrhotic patients. The serum creatinine level frequently failed to rise above normal even when the glomerular filtration rate was very low (less than 25 ml/minute), and creatinine clearance overestimated inulin clearance by a factor of two in Group III patients. However, the creatinine index was an aid in determining true glomerular filtration rate and may be a useful clinical test in the evaluation of renal insufficiency in cirrhotic patients with normal serum creatinine values. Many patients with cirrhosis and ascites will have a glomerular filtration rate of less than 60 ml/minute but a normal serum creatinine level. These patients may constitute a previously unrecognized large group.

Course of renal function in IgA glomerulonephritis in children and adolescents.

The pathophysiology of IgA GN was investigated in different stages of the disease. Seventeen patients who were between 3.5 and 16.5 years of age at the onset were included in the study. Clearance studies were performed repeatedly in 6 patients (in 5 of them over a period extending from the onset to 5-9.5 years) and only once in 9 patients (10-23 years after the onset). Two patients (one with uremia) were only evaluated clinically. CIn, CPAH and UNaV were studied during hydropenia (HP) and 3% isotonic saline volume expansion (VE). Shortly after the onset CIn, CPAH and UNaV were depressed. Renal function was essentially normal and 1 and 2 years after the onset in spite of signs of active disease. A supernormal GFR was found in 7 patients after they had had the condition between 5 and 17 years. After a duration of IgA GN for greater than 9 years 3 of 12 patients had developed hypertension and uremia and 2 had hypertension or labile BP. Three of 10 patients had a normal GFR and BP, but had increased natriuresis during VE. Only 2 of 10 patients were normotensive and had normal renal function. Disturbances in the renal function are thus frequent in all stages of IgA GN and the changes seem to be related to the duration of the disease. Exaggerated natriuresis may indicate progressive disease.

The influence of disseminated intravascular coagulation on renal function after experimental hemorrhagic shock.

Abstract Experiments were performed to investigate the influence of disseminated intravascular coagulation (DIC) during shock upon renal function after shock. Hemorrhagic hypotension of 2 h duration at 50 mmHg was induced in anesthetized non-heparinized dogs, followed by reinfusion of shed blood (shock group 1). In shock group 2, acute splenectomy was performed prior to hemorrhage and epsilon-amino caproic acid was infused during hemorrhagic hypotension. In shock group 1, during hemorrhagic hypotension the whole blood clotting time and thrombin time shortened (hypercoagulability), the arterial platelet count increased and intrarenal platelet retention was observed. The results of renal function measurements reproduced the well known pattern of renal dysfunction after hemorrhagic shock in dogs: reduction of CPAH to about 55% and of CI to about 70% of pre-shock levels, significant increases of VU, ENa, E F Na (diuresis and natriuresis), decreases of U P Osm and TH2Oc and increase of V U C I and C Osm C I (disturbance of concentrating mechanism). Dogs in shock group 2 developed prolongation of whole blood and plasma clotting times (hypocoagulability), decrease in platelet count and factors V and VIII activity (factor depletion), and increases in titers of FDP (staphylococcal clumping test assay) and fibrin monomers (protamine sulfate test assay). Clotting changes were consistent with the diagnosis of DIC. After reinfusion, a different renal dysfunction pattern was observed: CPAH and CI were both reduced to about 35% of their pre-shock levels and CI as well as EI and EPAH were significantly lower than in shock group 1 and the increase of urine output did not occur. The depression of renal function and urine excretion following shock with DIC could be explained by pronounced cortical ischemia and reproduced the characteristic features of the acute renal failure in man (depression of EPAH, low CI, reduction of C I TRPF , decrease of U P Osm and TH2Oc). It is concluded, that coagulation derangements in addition to vasoconstriction during shock determine the course of renal function after shock and play an important role in the pathogenesis of shock kidney.

Drug Kinetics in Burn Patients

Thermal trauma reportedly induces a spectrum of intricate physiological alterations that often involve cardiovascular, hepatic, renal, and dermatological functions. Individual responses to varying degrees of burn and secondary complications may produce unpredictable changes in the pharmacokinetics of drugs. A number of reports describing the disposition of aminoglycoside antibiotics in burn patients have demonstrated clinially significant alterations in the pharmacokinetics of this class of drugs. Several authors have found significantly reduced serum half-lives in burn patients as compared with average values in non-burned subjects. Increased aminoglycoside clearances in some burn patients have been attributed to increased glomerular filtration secondary to elevated cardiac output, prostaglandin formation, and glucagon secretion: others attribute this to enhanced elimination of drug across damaged skin tissue. Monitoring of serum aminoglycoside concentrations is recommended because of the low therapeutic index of these agents and the variable course of renal function following burn injury. Topical application of mafenide acetate, providone iodine, and gentamicin to burn wounds has resulted in varying amounts of systemic absorption. Various systemic toxicities have been attributed to these topical therapies, especially in patients with compromised renal function. The extent and area of the burn, degree of hydration, and the amount of drug applied are factors influencing transcutaneous absorption. Sulphonamide derivatives are excreted in the urine subsequent to the application of silver sulphadiazine cream, but silver ions appear to be localised on surface tissue and are thus unavailable to the subeschar space. Additional studies are needed to characterise the pharmacokinetics of medications commonly administered to burn patients. Unfortunately, the marked variability and fluctuations in pathophysiological status following burn trauma often confound the interpretation of such kinetic investigations.

Considerations on the worthful recovery of renal function in hydronephrosis

We understand the term “worthful recovery” as that the kidney recovers to such an extent that it has the ability of maintaining healthy life by itself alone when the mate kidney happens to be severely damaged or removed in the future.In this study, we have clinically studied the limitation of the preoperative renal function which promises the worthy recovery after surgery for removing obstruction in hydronephrosis. In other words, we have studied the indication of kidney conservative operation in hydronephrosis from the functional viewpointFor the examination of the renal function, clearances of PAH, intrinsic inuline and osmorality were mainly employed.In Tab. 1 clearances in healthy male adults are shown. Results in various degree of hydronephrosis are shown in Tab. 2. To know the tendency of renal function of each degree of hydronephrosis the average values are entered. Here, errors due to dead space of enlarged renal pelvis must naturally be considered: the larger the dead space, the greater the error.To know the lower limit of renal function which can sustain healthy life we examined 3 groups of patients: chronic nephritis (Tab. 3), acquired healthy solitary kidney (Tab. 4) and nephrostomized hydronephrotic solitary kidney (Tab. 5). From the lowest values of clearance in these groups we found that the very limitation of renal function was as shown in Tab. 6.For obtaining the data on renal function as exactly as possible in hydronephrosis, with least trouble due to the dead space, we performed nephrostomy for collecting urine. Since it was confirmed by us that the kidney reached an almost stable state 2 weeks to 20 days after nephrostomy (we called it “shortly after”) we evaluated the possibility of the worthful recovery from the renal functions at this stage.Between the clearances and RA-ratio (relation of the size of renal artery to that of abdominal aorta at the level of branching of the latter) there was only a slight correlation ((Figs. 4, 5, 6).In B-grade hydronephrosis (low degree) renal functions shortly after nephrostomy were far above the above mentioned limitation (Tab. 7) and all of the cases recovered well as expected (Fig. 7, for instance). In D-grade (middle degree) hydronephrosis renal functions shortly after nephrostomy were not under the limitation (Tab. 6) and also recovered satisfactorily. In E-grade (high degree) hydronephrosis, in which the indication of conservance of the kidney should be earnestly discussed (Tab. 9), only 2 of 6 cases recover ed satisfactorily. The renal functions shortly after nephrostomy were in these 2 cases above or around the limitation.From the clinical estimations in hydronephrosis we are sure that the above mentioned limitation of renal functions for healthy life can be applicable for selecting the indication of conservative operation of hydronephrosis. If the renal functions shortly after nephrostomy below the limitation, saving the kidney is not worthwhile.Two cases of interest are here demonstrated: Case 1, 32 yrs male. Advanced hydronephrosis and hydroureter with vesico-ureteral reflux in acquired solitary kidney. Cystography reveals the condition well (Fig. 1). Renal functions following the indwelling catheterization of the bladder are shown in Fig. 2. He is healthy thereafter. As to the consideration of error due to dead space in this case, clearances of 1 hour and 24-hour's examinations are shown in Fig. 3.Case 2. (6th case in Tab. 9). 18 yrs male. E-grade hydronephrosis as shown in Figs. 8 and 9. On nephrostomy we found that about thick the half of the kidney became thin to 1 to 2mm thick and the remaining parenchyma was not more than 1cm thick. But, the renal functions shortly after nephrostomy were over the limitation, which rendered us to conserve the kidney. The course of renal function after nephrostomy is shown in Fig. 10. Pyelo-uretero-plasty brought good results in renal function.