Non diabetic kidney disease. Modeling long-term diabetes and related complications in rats
Search Menu Abstract Background. Remikiren is an orally active renin inhibitor with established antihypertensive efficacy.
As a single dose it induces renal vasodilatation, suggesting specific renal actions. Data on the renal effects of continued non diabetic kidney disease by renin inhibition are not available, either in subjects with normal, or in subjects with impaired renal function.
The effect of 8 days of treatment with remikiren mg o. Remikiren induced a significant peak fall in mean arterial pressure of Continued treatment with remikiren induced a sustained fall in blood pressure, renal vasodilatation, negative sodium balance, and a reduction in glomerular protein leakage. These data are consistent with a renoprotective potential of renin inhibition.
When administered systemically, renin inhibitors reduce blood pressure in healthy volunteers and hypertensive patients more or less similarly to ACEi [ 4—7 ].
Modeling long-term diabetes and related complications in rats J Pharmacol Toxicol Methods. Mar-Apr ; Epub Nov Gyömrői út
The renal haemodynamic actions of renin inhibitors so far have been consistent with a renoprotective potential. Remarkably, in accordance with earlier animal data [ non diabetic kidney disease16 ], the renal vasodilator response to renin inhibition was reported to exceed the response to ACE inhibition [ 17 ].
As the insulin dependent diabetes mellitus type 2 icd 10 application of renin inhibitors has been hampered by their low bioavailability, the experience with these compounds during maintenance treatment in man is very limited.
No data are available thus far on the renal effects of continued treatment with remikiren, or on the renal effects of renin inhibition in patients with renal function impairment and proteinuria. In the present study, therefore, we report on the renal and systemic effects of continued treatment for 8 days the renin inhibitor remikiren in hypertensive patients with normal renal function, as well as in patients with impaired renal function and proteinuria. Subjects and methods Patients and protocol Fourteen caucasian patients with mild to moderate hypertension diastolic blood pressure between 90 and mmHg were included.
No other clinical relevant target organ damage was allowed. All subjects gave their informed consent and the study was approved by the Ethical Committee of the Hospital.
Median age of the patients was 53 years range 32— The median body mass index at baseline was Histological diagnoses were glomerulosclerosis 3 ; membranous glomerulopathy 2and IgA nephropathy 1.
Systolic blood pressure at entry was ±2 mmHg range — and diastolic blood pressure was ±2 mmHg range 90— ; these values were similar for the essential hypertensives and the renal patients.
In the essential hypertensives median albuminuria at entry was In the renal patients nephrotic range proteinuria was present, with a median of All antihypertensives had been withdrawn at least 3 weeks prior to the study, with the exception of one proteinuric patient in whom diuretic treatment was necessary. The dose of the diuretic was kept constant throughout the protocol.
This patient was excluded from the analysis of electrolyte balance. During hospitalization they received a diet containing 50 mmol sodium, mmol potassium, 60 g protein, and ml fluids daily.
Chronic Kidney Disease (CKD) Pathophysiology
During this baseline period, stabilization of blood pressure, proteinuria, and electrolyte excretion was established. Subsequently, remikiren treatment mg orally o.
Blood pressure was measured daily between 11 and 12 a. Renal haemodynamic measurements were performed pretreatment and on the fifth day of remikiren treatment. On the first and the last treatment day timed blood samples were drawn for measurement of plasma renin activity PRAimmunoreactive renin irRand angII.
For each hour the mean value was calculated. Urinary protein was measured by the pyrogallol red—molybdate method.
This method has a coefficient of variation of During analysis plasma was first separated from plasma proteins by ethanol extraction. The lower limit of detection is 3.
Circulating levels of remikiren were determined by the radioinhibitor assay of Cumin et al. Glomerular filtration 1rate GFR and effective renal plasma flow ERPF were measured as the renal clearances of constantly infused [I]iothalamate and [I]hippuran respectively.
Correction for urine collection errors was applied as described previously [ 19 ].
Values are normalized for body surface area. Data analysis Results are presented as means±SEM.
This discovery could lead to a test that would help doctors identify patients at greatest risk and help them potentially avert the disease through interventions including diet and exercise.
Data sets that are not normally distributed are presented as medians and ranges. Data on hormonal responses, blood pressure, renal haemodynamics, and electrolyte balance are presented for all patients taken together. Data on the responses of proteinuria and albuminuria are presented for the renal patients and the essential hypertensives separately.
Results The efficacy of remikiren in blocking the RAS, as well as the drug levels, are shown in Figure 1. PRA fell maximally within 30 min after the first dose of remikiren and remained suppressed during the 12 h following.
After dosing, a further decrease to almost undetectable levels occurred.