Topic Discussion: What causes glomerulomegaly?

What causes glomerulomegaly?

Congenital cyanotic heart disease
Cor pulmonale
Obesity and Sleep apnea
Sickle cell disease
Polycythemia vera
Alcoholism
Hepatic steatosis
Cystic fibrosis

What is the most common physiological abnormality in all of the above

Hypoxemia! Perhaps a combination of metabolic demands of some of these illnesses, hypertrophy of the erythropoietin producing cells, passive congestion causes in the systemic circulation and increased viscosity all might be leading to glomerular damage and proteinuria as a result.

What does glomerulomegaly mean on pathology?

There is going to be focal and diffuse hypercellularity, segmental or global sclerosis, mesangial thickening
Vessels:- capillary congestion, hyalinization of afferent and efferent arterioles
Tubular atrophy
Interstitial Fibrosis

Reference: http://www.ncbi.nlm.nih.gov/pubmed/9402101

TOPIC Discussion: Hypertension as risk factor for Renal Cell Cancer

We know that smoking increases risk of renal cell cancer. It is interesting to note that a study published more than 10 years ago in NEJM showed the risk of Obesity and HTN as a risk factor for renal cell cancer.

The study had looked at over 300,000 Swedish men who had physical exams done in 1970s and 1990s and followed till 1995.  Renal cell cancer patients were identified and risks were analyzed. Higher body-mass index and elevated blood pressure independently increase the long-term risk of renal-cell cancer in men. A reduction in blood pressure lowers the risk.

While obesity and lot of things are an enigma, the association with HTN is concerning.  Most of the anti cancer agents in RCC are anti VEGF or Tyrosine kinase inhibitors and it is possible that the HTN in this case is might be associated elevations of such factors and leading to renal cancer.  Does HTN leading to CKD then predispose one to getting renal cancer? These are some interesting findings. Nevertheless, it’s an observational study with only Swedish Men and cannot be generalized at all. 

What else is out there regarding this association of HTN and renal cell cancer?

A Japanese study called the JACC study found nine risk factors (i.e., smoking, obesity, low physical activity, hypertension, diabetes mellitus, kidney diseases, beef intake, fondness for fatty food and black tea) in a Japanese population.

Another study done in the US looked at risk factors for RCC. Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease in their study.  Another study published in the Urology journals puts HTN as a risk factor. VITAL study found a significant association of renal cell carcinoma with obesity, smoking, hypertension, renal disease and viral hepatitis.

Now here is a study that doesn’t feel that HTN is a risk factor for RCC.

 It is quite possible that is the constellation of metabolic syndrome that leads to this RCC risk. Given the risk factors that are consistently being similar to risk factors for cardiac disease, it is more likely that the metabolic syndrome might be the major culprit. The rise of incidence in RCC that we have seen in the last 2 decades goes in line with the rise of the metabolic syndrome and obesity. 

IN the NEWS: Obesity and organ donation

Obese uremic patients might be the next wave of patients that nephrologists will face. A recent editorial in NDT highlights this epidemic that we are starting to see. Transplantation becomes a challenge in that setting as well. But what about donors? Where is the cut off and what are centers doing?

A recent study published in Clin Transplantation presents their data on a single center looking at obese donors. Of the 104 donors that the center evaluated in that time frame, only 18% had a normal body mass index (BMI) of <25.  Over 80% of the donors spanned the overweight to morbidly obese classifications. There were a total of 23 donors (22%) who were considered moderately and morbidly obese (BMI >35).
Of these, only three (13%) succeeded at losing weight and donating.

Some key points:
1. Only 18% had normal BMI!!!! ( hence most donors are in the overweight to obese spectrum)
2. Cut off for BMI at many centers vary, some have 35 for donors and some have 30( which would turn away even more donors)
3.Given national trend of obesity, this is going to get even more worrisome.
4.Follow ups: Six-month follow-up of obese donors post donation
did not show a significant difference  between obese donors and their non-obese counterparts
with respect to estimated glomerular filtration rate or creatinine from baseline in one study.
5.Another study showed that obesity at the time of donation was associated with dyslipidemia and hypertension, two important cardiovascular risk factors, although they were not found to be exacerbated by donation.
6.Obesity may be a frequent barrier to living kidney donation, directly leading to exclusion as a potential kidney donor in about one in five instances. Successful weight loss leading to donation appears to be infrequent, suggesting need to address obesity in the donor population.