Renin inhibition in the treatment of diabetic kidney disease

2013 ◽  
Vol 124 (9) ◽  
pp. 553-566 ◽  
Author(s):  
Radko Komers
Keyword(s):  
Kidney Diseases ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Limiting Step ◽  
Renin Inhibition ◽  
Raas Inhibitors ◽  
Stage Renal Disease ◽  
End Stage ◽  
Activation Cascade

Inhibition of the RAAS (renin–angiotensin–aldosterone system) plays a pivotal role in the prevention and treatment of diabetic nephropathy and a spectrum of other proteinuric kidney diseases. Despite documented beneficial effects of RAAS inhibitors in diabetic patients with nephropathy, reversal of the progressive course of this disorder or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. Incomplete inhibition of the RAAS has been postulated as one of reasons for unsatisfactory therapeutic responses to RAAS inhibition in some patients. Inhibition of renin, a rate-limiting step in the RAAS activation cascade, could overcome at least some of the abovementioned problems associated with the treatment with traditional RAAS inhibitors. The present review focuses on experimental and clinical studies evaluating the two principal approaches to renin inhibition, namely direct renin inhibition with aliskiren and inhibition of the (pro)renin receptor. Moreover, the possibilities of renin inhibition and nephroprotection by interventions primarily aiming at non-RAAS targets, such as vitamin D, urocortins or inhibition of the succinate receptor GPR91 and cyclo-oxygenase-2, are also discussed.

scholarly journals A Review of the Potential Benefits of Pentoxifylline in Diabetic and Non-Diabetic Proteinuria

2011 ◽  
Vol 14 (1) ◽  
pp. 128 ◽  
Author(s):  
Shirinsadat Badri ◽  
Simin Dashti-Khavidaki ◽  
Mahboob Lessan-Pezeshki ◽  
Mohammad Abdollahi
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Large Scale ◽  
Kidney Diseases ◽  
Scientific Basis ◽  
Sustained Reduction ◽  
Number Of Patients ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease (ESRD). Decreasing proteinuria is the mainstay of therapy in order to delay the progression of CKD. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to ESRD. Pentoxifylline (PTF) is known for its potent inhibitory effects against cell proliferation and inflammation which play important roles in CKD progression. Data derived from both human studies and animal models demonstrated that PTF has broad-spectrum renoprotective effects and therefore, provide a scientific basis for the use of PTF as an anti-proteinuric agent. Conclusion of this review is that short-term use of PTF may produce a significant reduction of proteinuria in subjects with diabetic and also non-diabetic kidney diseases but the reports of long-term use of PTF also show that urinary protein excretion exhibits a progressive and sustained reduction in patients treated with PTF. Whether the long-term use of PTF could be a pharmacological alternative for delaying or preventing the development of end stage renal disease, is among the questions that remained to be appropriately answered in large-scale clinical trials.

scholarly journals Changes of MicroRNA-377 in Diabetic Nephropathy

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H A Elshinnawy ◽  
C R Kamel ◽  
M H A Elkeleng
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Patients ◽  
Ckd Stage ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Stage Renal Disease ◽  
End Stage ◽  
Stage 1

Abstract Background as one of the most important long term complications of diabetes, Diabetic nephropathy is the major cause of end stage renal disease and high mortality. Purpose to identify the pattern of microRNA-377 changes specific for diabetic nephropathy in diabetic patients and in patients with chronic kidney disease of different etiology. Patients and Methods the study was conducted from 2016 to 2018, included 50 patients for analysis of MicroRNA-377 and its control gene U18 at El Demrdash Hospital Ain shams university and Quessena Hospital El Monfia. The miRNA-U18 was analyzed for normalization of correction ratio. Results the results of our research found that the highest median IQR of miR-377 was significantly present in DN stage 1&2 and the lowest median IQR was significantly present in CKD stage 1&2, and there was significant difference between group 1 (DN stage 1&2) versus group 2 (DN stage 3&4), group 3 (Diabetics without nephropathy) and all stages of CKD. Conclusion in diabetic nephropathy stage 1&2, serum miR-377 was highly significant increased more than diabetics without nephropathy, diabetic nephropathy stage 3&4 and all satges of CKD.

Abstract 370: Contrast-Induced Nephropathy and Long-Term Outcomes in Patients With Diabetes Undergoing Coronary and Peripheral Angiography and Intervention

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Dennis A Hopkinson ◽  
Samuel P Powell ◽  
Raveen Chawla ◽  
Wendy Bottinor ◽  
Jeremy S Turlington ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Long Term Outcomes ◽  
Peripheral Angiography ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage

Background: Patients with diabetes may be at increased risk of contrast-induced nephropathy (CIN) when undergoing coronary and/or peripheral angiography or intervention but there is little data on long-term outcomes. We examined the relationship between diabetes, CIN and long-term outcomes in patients undergoing coronary and/or peripheral angiography and intervention. Methods and Results: We studied 4070 consecutive, predominantly (98%) male patients undergoing coronary and peripheral angiography and intervention and assessed the association between diabetes, CIN and long-term outcomes including renal dysfunction at 3 months, the need for dialysis and mortality. The mean age of the patients was 66.6 years. Approximately two fifths of the patients (n=1671, 41.05%) were diabetic. Patients with diabetes were the same age but had higher baseline creatinine compared to the patients without diabetes. CIN occurred in 70 (4.19%) diabetic patients and in 64 (2.67%) patients without diabetes at 72 hours after the procedure (odds ratio [OR] 1.59; 95% confidence interval [CI] 1.13 - 2.25; P=0.008). At 3 months, renal dysfunction was seen in 179 (10.71%) diabetic patients versus 174 (7.25%) of the non-diabetic group (OR 1.53, CI 1.23 - 1.91; P=0.0001). After a follow-up of 5 years, 31 (1.86 %) patients with diabetes had developed end-stage renal disease and were started on dialysis versus 13 (0.54 %) of the non-diabetic group (OR 3.47, CI 1.81 - 6.65; P<0.0001). 478 (28.61 %) patients of the diabetic group had died versus 479 (19.97 %) of the non-diabetic group (OR 1.61, CI 1.39 - 1.86; P<0.0001). On multivariate analysis, after adjustment for age, comorbidities, medical therapy and baseline creatinine, the presence of diabetes was significantly associated with CIN (OR 1.50, CI 1.06 - 2.43: p=0.02) and was significantly associated with the incidence of end stage renal disease requiring dialysis (OR 3.64, CI 2.07-10.04; P<0.0001) and with mortality at 5 years (OR 1.58, CI 1.42-2.03, P<0.0001). Conclusion: In this cohort of patients undergoing coronary and/or peripheral angiography and intervention diabetes was associated with CIN, with end-stage renal disease and the need for hemodialysis and was associated with an increased mortality.

scholarly journals Depression among Chronic Kidney Diseases Patients Receiving Hemodialysis

2020 ◽  
Vol 3 (2) ◽  
pp. 73-79
Author(s):  
Shanti Khadka ◽  
Rita Adhikari ◽  
Tarun Paudel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Cross Sectional ◽  
Prevalence Of Depression ◽  
Depression Level ◽  
Western Regional ◽  
Stage Renal Disease ◽  
End Stage

Background: Chronic Kidney Disease (CKD) is a progressive irreversible loss of renal function over a period of months or years. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintains life. Hemodialysis is used for patients who require short term dialysis (days to weeks) and for patients with advanced CKD and End Stage renal Disease (ESRD) who require long term or permanent renal replacement therapy. Hemodialysis significantly and adversely affects the lives of patients, both physically and psychologically. Depression is the most common psychological condition among patients with ESRD. Depression in dialysis patients not only effect mortality, but increased rate of hospitalizations and dialysis withdrawal is also very common. Methods: A descriptive cross sectional research design was carried out to identify the depression level of chronic kidney disease patients receiving Hemodialysis in Western Regional Hospital, Pokhara using Beck Depression Inventory among forty six patients. Results: The study findings revealed that majority of the patients (84.8%) has various degree of depression i.e. mild (21.7%), moderate (30.8%) and severe (32.6%). Only fifteen percent of patient has no depression. There was no statistical association between the level of depression and socio-demographic variables. It can be concluded that the prevalence of depression is high among patients receiving Hemodialysis. Conclusion: The prevalence of depression is high among patients receiving Hemodialysis. It is effective to provide mental health services to the CKD patients receiving Hemodialysis which help them better psychologically adaptation to their disease and improve their quality of life.  

scholarly journals Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

2020 ◽  
Vol 21 (11) ◽  
pp. 3798 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
José Luis Morgado-Pascual ◽  
Lucas Opazo-Ríos ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Intracellular Signaling ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Number Of Patients ◽  
Close Relationship ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

scholarly journals Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease

2016 ◽  
Vol 310 (10) ◽  
pp. R877-R884 ◽  
Author(s):  
Radko Komers ◽  
Horacio Plotkin
Keyword(s):  
Structural Changes ◽  
Kidney Diseases ◽  
Angiotensin Receptor Blockers ◽  
Experimental Studies ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Stage Renal Disease ◽  
End Stage ◽  
New Treatments

Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients. Inhibition of endothelin (ET) system in combination with established RAASis may represent such an approach. There are complex interactions between both systems and similarities in their renal physiological and pathophysiological actions that provide theoretical rationale for combined inhibition. This view is supported by some experimental studies in models of both diabetic and nondiabetic CKD showing that a combination of RAASis with ET receptor antagonists (ERAs) ameliorate proteinuria, renal structural changes, and molecular markers of glomerulosclerosis, renal fibrosis, or inflammation more effectively than RAASis or ERAs alone. Practically all clinical studies exploring the effects of RAASis and ERAs combination in nephroprotection have thus far applied add-on designs, in which an ERA is added to baseline treatment with ACEIs or ARBs. These studies, conducted mostly in patients with diabetic nephropathy, have shown that ERAs effectively reduce residual proteinuria in patients with baseline RAASis treatment. Long-term studies are currently being conducted to determine whether promising antiproteinuric effects of the dual blockade will be translated in long-term nephroprotection with acceptable safety profile.

Frequency of Gastrointestinal Diseases in Patients with End-Stage Renal Disease Treated with Long Term Dialysis

2018 ◽  
Vol 2 (2) ◽  
pp. 105-112
Author(s):  
Lutfi Zylbeari ◽  
Zamira Bexheti ◽  
Gazmend Zylbeari ◽  
Ferizate Haxhirexha ◽  
Kastriot Haxhirexha
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Gastrointestinal Diseases ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups

2021 ◽  
Author(s):  
Geir Mjøen ◽  
Umberto Maggiore ◽  
Nicos Kessaris ◽  
Diederik Kimenai ◽  
Bruno Watschinger ◽  
...  
Keyword(s):  
Evaluation Process ◽  
Kidney Donation ◽  
Kidney Donors ◽  
Living Kidney Donors ◽  
Relative Risks ◽  
Written Information ◽  
The Difference ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. Methods All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. Results The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. Conclusions The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

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