Another Study On Obesity And Kidney Disease

It should come as no surprise that obesity contributes to chronic kidney disease as explained in this paper.  Abstract:

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

Nephrolithiasis is the formation of kidney stones, which are quite painful (I have had them). Chronic kidney disease and kidney cancer are obviously key effectors of morbidity and mortality and anything we can do – including maintaining a healthy body weight – to avoid such outcomes would be well worth it.

Overestimating Chronic Kidney Disease Frequency?

The frequency of chronic kidney disease may be overestimated due to not taking into account the normal decline in kidney function with age.  You’d think doctors, particularly nephrologists, would all know to make the necessary adjustments or normality for older patients, but apparently not. Abstract:

The process of glomerular filtration of plasma fluid has been known for over 160 years and the measurement of the rate of its formation (glomerular filtration rate, GFR) has been possible for over 80 years. Studies conducted in the 1930's to the 1950's clearly established that GFR declines, perhaps inexorably, with normal ageing, usually beginning after 30-40 years of age. The rate of decline may accelerate after age 50-60 years. This decline appears to be a part of the normal physiologic process of cellular and organ senescence and is associated with structural changes in the kidneys. In the last decade a new paradigm has been introduced in which the true or measured GFR is estimated (eGFR) by formulas based on serum creatinine levels and in which these estimates are applied to the diagnoses of chronic kidney disease (CKD) in the general population. These criteria for diagnosis of CKD include an absolute threshold for eGFR, unadjusted for the effects of age on the normal values for eGFR. A consequence of these criteria has been to overstate the frequency of CKD in the general population and to generate many "false positive" diagnoses of CKD. This paper discusses the known effects of ageing on GFR and the consequences of using a classification system for defining CKD that does not take into account the normal decline of GFR with ageing.

Against Fibrosis

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8674830

Fibrosis, a disorder characterized by formation of excess connective fibrous tissue, is common in various disease states, including cardiovascular and kidney disease, negative affecting the function of these organs.  A new study suggests that inhibition of interleukin 11 signaling can repress fibrosis formation and can serve as a possible therapy for fibrotic disease.  Abstract:

Fibrosis is a final common pathology in cardiovascular disease1. In the heart, fibrosis causes mechanical and electrical dysfunction1,2 and in the kidney, it predicts the onset of renal failure3. Transforming growth factor β1 (TGFB1) is the principal pro-fibrotic factor4,5 but its inhibition is associated with side effects due to its pleiotropic roles6,7. We hypothesised that downstream effectors of TGFB1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicities. Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These data reveal a central role of IL11 in fibrosis and we propose inhibition of IL11 as a new therapeutic strategy to treat fibrotic diseases.

Nephrolithiasis In Children

By Robert R. Wal - http://en.wikipedia.org/wiki/Kidney_stone, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3101185

Kidney/urinary stone disease is a serious disorder, and this paper discusses dietary interventions to avoid this disease in children.  As the abstract below makes clear, there hasn’t been any real positive findings apart from some limited data in favor of oral potassium citrate supplementation.  I have had kidney stones myself; that was one of the most painful experiences of my life.  Upon advice from an urologist, my own major preventive technique is drinking a lot of water during the day (up to 2 liters per day or more).  That’s inconvenient of course – what goes in must come out – and requires many bathroom visits per day.  A problem with children is that they go to school and can’t be spending much time in the bathroom, and keep in mind that drinking too much water can be a problem, and children, with smaller bodies than adults, have to be more careful with that.  The bottom line: follow your doctor’s advice on this subject, for both adults and children. Speaking only for myself as an adult, drinking water has helped, and I also eat a healthy diet as well.  Abstract:

BACKGROUND:

Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium.

OBJECTIVES:

To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years.

SEARCH METHODS:

We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions.

SELECTION CRITERIA:

Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children.

DATA COLLECTION AND ANALYSIS:

We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE.

MAIN RESULTS:

The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision.We found no information on retreatment rates.

SECONDARY OUTCOMES:

We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation.We were unable to perform any preplanned secondary analyses.

AUTHORS' CONCLUSIONS:

Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.