Effects of PPARγ on hypertension, atherosclerosis, and chronic kidney disease

Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear hormone receptor that is trans-activated by its ligands including insulin-sensitizing thiazolidinediones. PPARγ has recently been reported to demonstrate pleiotropic beneficial effects in the vasculatures, independent of its blood glucose-lowering effects. Firstly, PPARγ ligands have been shown to lower blood pressure in both animals and human. The effect may possibly be mediated via the PPARγ-mediated inhibition of the angiotensin (Ang) II type 1 receptor expression as well as Ang II-mediated signaling pathways, which may result in the suppression of the renin-angiotensin system (RAS). Secondly, the progression of atherosclerosis was also prevented by PPARγ ligands in both animals and human. In addition to the PPARγ-mediated suppression of the RAS and the thromboxane A(2) system, protective effects of PPARγ ligands on endothelial function may also be involved. Thirdly, reno-protective effects of PPARγ ligands, especially on reducing urinary albumin, have been observed in both animals and human not only in diabetic nephropathy but also in non-diabetic renal diseases. The reno-protective effects may be mediated, at least in part, via the PPARγ ligand-induced blood pressure-lowering effects, protective effects on endothelial function, and vasodilating effects on the glomerular efferent arterioles. Additionally, anti-cancer effects of PPARγ ligands have recently been reported. Taken together, usefulness and effectiveness of PPARγ ligands on lifestyle related diseases will be increasingly appreciated.     

Arrhythmias,chronic kidney disease and the elderly:a triple jeopardy

Crdiovascular diseases (CVD) incur a heavy burden of morbidity and mortality among patients with chronic kidney disease (CKD), particularly among the elderly. It is estimated that about 22-25% of all adults beyond the age of 65 years have moderate or severe renal dysfunction. Traditional risk factors such as hypertension, hypertriglyceridemia, low HDL levels and physical inactivity have a stronger association with cardiovascular mortality; however this association is weaker with risk factors such as high CRP, fibrinogen, interleukin 6 (IL-6), factor VIIIc and lipoprotein(α) which are novel for patients with CKD.     

Does treating obesity stabilize chronic kidney disease?

Background

Much epidemiological evidence suggests that hydrocarbon exposure may induce glomerulonephritis and worsen its course in many patients. The mechanisms are unknown, however, no specific microscopic pattern has been identified, and it has also been argued that hydrocarbon exposure causes tubular damage mainly. Studying experimental animals may best answer these questions, and as no systematic review of glomerulonephritis produced experimentally by hydrocarbon exposure has been performed previously, I found it relevant to search for and analyse such studies.

Methods

Animal experiments having mimicked human glomerulonephritis by hydrocarbon exposure were sought on Medline and Toxnet

Results

Twenty-six experiments using thirteen different hydrocarbons were identified. Several human subtypes were observed including IgA nephritis, mesangial, proliferative and extracapillary glomerulonephritis, focal and focal-segmental sclerosis, minimal change nephropathy, anti-GBM and anti-TBM nephritis, and glomerulonephritis associated with peiarteritis nodosa. Glomerular proteinuria was seen in 10/12 experiments that included urine analyses, and renal failure in 5/8 experiments that included measurements of glomerular function. All experiments resulted in various degrees of tubular damage as well. In most studies, where the animals were examined at different times during or after the exposure, the renal microscopic and functional changes were seen immediately, whereas deposits of complement and immunoglobulins appeared late in the course, if at all.

Conclusion

These experiments are in accord with epidemiological evidence that hydrocarbon exposure may cause glomerulonephritis and worsen renal function. Probable mechanisms include an induction of autologous antibodies and a disturbance of normal immunological functions. Also, tubular damage may increase postglomerular resistance, resulting in a glomerular deposition of macromolecules. In most models a causal role of glomerular immune complex formation was unlikely, but may rather have been a secondary phenomenon. As most glomerulonephritis subgroups were seen and as some of the hydrocarbons produced more than one subgroup, the microscopic findings in a patient cannot be used as a clue to the causation of his disease. By the same reason, the lack of a specific histological pattern in patients with glomerulonephritis assumed to have been caused by hydrocarbon exposure is not contradictive.     

Anaemia, diabetes and chronic kidney disease: where are we now?

Anaemia is a common finding in people with diabetes and chronic kidney disease and failure of the kidney to produce erythro-poietin in response to a falling haemoglobin concentration is a key component, correlating with the degree of albuminuria, renal dysfunction and iron deficiency. Anaemia in diabetes is associated with a number of adverse outcomes, including increased risk of all cause and cardiovascular mortality. Whether or not anaemia is a marker or mediator of adverse outcome still remains to be completely resolved. Treatment of anaemia in diabetes has quality of life benefits and reduces transfusion requirements. Correction of anaemia to normal haemoglobin concentrations is associated with significant adverse cardiovascular outcomes and is not recommended, escalating doses of erythropoiesis-stimulating agents should be avoided. The treatment of anaemia in people with diabetes and chronic kidney disease should begin with optimisation of iron stores. An aspirational haemoglobin concentration range of 10-12 g/dl with anaemia management, balances proven benefits of anaemia treatment with potential cardiovascular risk.     

Concordance between modification of diet in renal disease,chronic kidney disease epidemiology collaboration and Cockcroft-Gault equations in patients with chronic kidney disease at St. Paul’s hospital millennium medical college,Addis Ababa,Ethiopia

Background

The most commonly used glomerular filtration rate estimating equations for drug dosing are Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. However there is still a concern about whether to use MDRD and CKD-EPI interchangeably with CG for drug dosage adjustment.

Methods

The study was initiated to determine the concordance between MDRD, CKD-EPI and CG equations and associated factors in patients with chronic kidney disease at Saint Paul’s Hospital Millennium Medical College (SPHMMC). This was a cross sectional study which involved patient chart review and physicians self-administered questionnaire. Serum creatinine level?≥?1.2 mg/dL was used as a cutoff point in pre-selection of patients. The correctness of the drug dose prescribed for the level of renal function were compared to the drug database (Lexi-Comp) available through Up-to-date version 21.2.

Results

Among the total of 422 patients, 249 (59%) were males. Mean age of patients was 46.09 years. The use of MDRD equation for drug dose adjustment by physicians working in the renal clinic of SPHMMC was six out of nine physicians. The Pearson correlation coefficient between the CG with MDRD and CKD-EPI equations was r?=?0.94, P?<?0.001 and r?=?0.95, P?<?0.001, respectively. The concordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories was 73.7%, Kappa?=?0.644 and 74.9%, Kappa?=?0.659, respectively. Concordance between the CG with MDRD and CKD-EPI equations for the drug dosing recommendation was 89.6%, kappa?=?0.782 and 92%, kappa?=?0.834, respectively. Age?>?70 years was associated with discordance between CG and MDRD equations for drug dosing recommendation whereas serum creatinine 1.2–3.5 mg/dL, weight?<?61 Kg and age?>?70 years were associated with discordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories. However, none of the factors associated with discordance between CG and CKD-EPI for drug dosing.

Conclusion

MDRD equation can be used interchangeably with CG equation for drug dosing recommended in all adult patients between the age of 18 and 70 years. CKD-EPI can be used interchangeably with CG in all adult Ethiopian patients with CKD.

     

Linking chronic kidney disease and Parkinson’s disease: a literature review

Chronic kidney disease (CKD) has been typically implicated in cardiovascular risk, considering the function the kidney has related to blood pressure, vitamin D, red blood cell metabolism, and electrolyte and acid-base regulation. However, neurological consequences are also attributed to this disease. Among these, recent large epidemiological studies have demonstrated an increased risk for Parkinson’s disease (PD) in patients with CKD. Multiple studies have evaluated individually the association of blood pressure, vitamin D, and red blood cell dysmetabolism with PD, however, no study has reviewed the potential mechanisms related to these components in context of CKD and PD. In this review, we explored the association of CKD and PD and linked the components of the former to propose potential pathways explaining a future increased risk for PD, where renin-angiotensin system, oxidative stress, and inflammation have a main role. Potential preventive and therapeutic interventions based on these associations are also explored. More preclinical studies are needed to confirm the potential link of CKD conditions and future PD risk, whereas more interventional studies targeting this association are warranted to confirm their potential benefit in PD.

     

Obesity--the risk factor of cardiovascular disease in patients with chronic kidney disease?

In general population obesity is regarded as a predisposing factor for chronic disease such as type 2 diabetes and cardiovascular disease. Obesity increases the risk of kidney disease and adversely affects the progress of kidney disease among patients with diagnosed kidney disease. The main reason of mortality in chronic kidney disease patients is cardiovascular disease, however, the real meaning of obesity as a risk factor of cardiovascular diseases is still uncertain. While in a general population obesity causes higher cardiovascular mortality, many studies reflect inverse association in chronic kidney disease patients. Obesity is associated with better survival, contrary to general population obesity appears to be a protective factor of cardiovascular disease. The name of this phenomenon is "reverse epidemiology" or "obesity paradox", in dialysis patients known as a "risk-factor-paradox". Some studies do not confirm this paradox association in patients with chronic kidney disease.     

Normoalbuminuric diabetic kidney disease: a distinct entity?

International Journal of Diabetes in Developing Countries -     

Polycystic kidney disease: will it become treatable?

Polycystic kidney disease is an inherited multisystem disorder. It causes progressive loss of kidney function, flank pain, urinary tract infection, arterial hypertension and vascular abnormalities. Until the present time the treatment of polycystic kidney disease has been symptomatic. New approaches based on cell culture of cyst wall epithelia and on the discovery of polycystins 1 and 2 have lead to novel treatment protocols to attack the origin of the disease. These protocols involve vasopressin antagonists, rapamycin and somatostatin at the present time.     

Diabetic kidney disease：Act now or pay later

For the 2010 International Society of Nephrology/International Federation of Kidney Foundations World Kidney Day Steering Committee~* ( RA ) and the International Diabetes Federation (PZ) World Kidney Day 11 March 2010: we must act on diabetic kidney disease In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called " Diabetes in the Kidney: Time to act"~([1]) to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. It aimed to alert governments, health organisations, providers, doctors and patients to the increasing health and socio-economic problems due to diabetic kidney disease and its sequelae, end stage kidney disease requiring dialysis and cardiovascular death. Seven years later, the same message has become even more urgent.     

Morphologic,mechanical and functional sonographic parameters of arteries in autosomal dominant polycystic kidney disease

Objective To investigate whether the risk factors of cardiovascular disease exist in early stage of ADPKD patients with normal renal function. Methods Morphologic , mechanical and functional sonographic parameters of arteries were examined by high-frequency ultrasonography in 32 hypertensive and 28 normotensive ADPKD patients with preserved renal function, 25 patients with es-     

Where does albuminuria come from in diabetic kidney disease?

The classic mechanism to explain albumin excretion in diabetes has been permeability defects in the glomerular filter. However, a new concept has emerged that albuminuria can be explained by the two major pathways the proximal tubular cell uses to process filtered albumin. Specifically, albumin permeability through the glomerular filter is only governed by size selectivity. Most of the filtered albumin is retrieved by the proximal tubular cell and returned to the peritubular blood supply. Albuminuria in the nephrotic range would arise from retrieval pathway dysfunction. The small quantities of filtered albumin that are not retrieved undergo obligatory lysosomal degradation before urinary excretion as small peptide fragments. This pathway is sensitive to metabolic factors responsible for hypertrophy and fibrosis, particularly molecules such as angiotensin II and transforming growth factor-β1, whose production is stimulated by hyperglycemic environments. Dysfunction in this degradation pathway may lead to albuminuria below the nephrotic range.