Diabetic nephropathy treatment guidelines 2021
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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 treatment 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, diabetic nephropathy treatment guidelines 2021 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 ].
The renal haemodynamic actions of renin inhibitors so far have been consistent with a renoprotective potential.
Remarkably, in accordance with earlier animal data [ 1516 ], the renal vasodilator response diabetic nephropathy treatment guidelines 2021 renin inhibition was reported to exceed the response to ACE inhibition [ 17 ]. As the clinical 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 diabetic nephropathy treatment guidelines 2021 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.
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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.
SGLT2-inhibitors – antihyperglycaemic agents with benefits beyond glucose control
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. 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.
Data sets diabetic nephropathy treatment guidelines 2021 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. Remikiren plasma levels reached their peak within 30 min after oral administration both on the first median Cmax Remikiren was rapidly cleared from the plasma thereafter. It shows that MAP fell significantly, from ±2 to 96±2 mmHg. The effect on diurnal blood pressure profile is given in Figure 3.
It shows that MAP is reduced throughout 24 h and that heart rate did not change. The fall in blood pressure was similar for systolic and diastolic blood pressure. This resulted in a trough to peak ratio of 0. The renal haemodynamic effects are shown for individual patients in Figure 4. Mean MAP was lowered from Remikiren exerted significant effects on the renal excretion of sodium and potassium Figure 5.
This negative sodium balance corresponded to a decrease in body diabetic nephropathy treatment guidelines 2021 of 0. During these 8 days, a transient fall in aldosterone was observed with a return to values not different from baseline as of day 4 Figure 5. The effect of remikiren on proteinuria in the six renal patients is shown in Figure 6together with the effect on MAP in these patients.
Median baseline value was 5. In the essential hypertensive patients a reduction in renal protein leakage was found as well. No significant effects on serum electrolytes, albumin or cholesterol were observed during treatment.
Bajcsy-Zsilinszky Kórház és Rendelőintézet, Budapest Summary SGLT2-inhibitors — antihyperglycaemic agents with benefits beyond glucose control SGLT2 sodium-glucose co-transporter -inhibitors were developed for treating patients with type 2 diabetes. Efficacy and safety of these drugs were documented in several phase 3 clinical trials. The position of SGLT2-inhibitors in the therapeutic approach for patients with type 2 diabetes were assigned in different guidelines and use of these drugs were suggested in dual or triple combination therapy after failure with metformin-monotherapy.
Mean arterial pressure mean±SEM during baseline and 8 days treatment with remikiren, mg o. Discussion Continued treatment for 8 days with renin inhibitor remikiren induced distinct systemic as well as renal effects in hypertensive patients with normal and impaired renal function.
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A fall in blood pressure was observed that is sustained throughout the day. GFR was unchanged, resulting in a fall in FF. Finally, a net negative sodium balance was observed, associated with a positive potassium balance. This dissociation is in line with previous studies [ 20 ].
The peak drug levels immediately after dosing as well as the rapid clearance from the plasma therafter confirms the pharmacokinetic profile of remikiren, as described earlier [ 91121 ]. Experimental data have shown that remikiren levels in tissue exceed those in plasma [ 2223 ]. It has been hypothesized that the kidney is the main target tissue for remikiren and that retention of the drug in this organ may provide a reservoir of drug within the body [ 23 ].
This would explain the sustained pharmacodynamic effects after single doses of remikiren despite undetectable plasma drug levels [ 8—10 ]. Thus it is likely, in spite of the low oral bioavailability, that enough drug is available at the target level.
We questioned whether an impaired renal function would lead to plasma accumulation of the drug.