August 2018

1) Transplanting kidneys from hepatitis C donors 

After revolutionizing the management of hepatitis C, DAAs (Directly Acting Antivirals) are all set to expand the donor pool in deceased donor kidney transplantation.  After the exciting report (reviewed previously in our June 2017 post) of successfully transplanting 10 kidneys from hepatitis C positive donors into hepatitis C negative recipients, THINKER 1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), authors report here the intermediate term data (12 months) on their cohort including additional 10 such patients. All 20 patients achieved HCV cure despite the use of intense immunosuppression (primary outcome), they also experienced improved quality of life as assessed by RAND 36.

Recipients of the HCV positive kidneys also had higher eGFR post-transplant at 12 months (median, 72.8 vs. 57.7 mL/ min/1.73 m2; CI for the between-group difference, 7.9 to 19.2 mL/min/1.73 m2) probably related to the younger age of deceased donors who are hepatitis c positive. A new chapter in expanding the donor pool indeed!

 

2) Copeptin in the evaluation of polyuria

 

Visual abstract by Divya Bajpai (@divyaa24)

In ‘hypotonic polyuria’ (these endocrinologists want to tease us- hypotonic polyuria is any polyuria that is not due to solute diuresis) water restriction test is often performed by endocrinologist at our center (they bother us twice: once by sending samples to our lab for osmolality measurements and later when they find themselves clueless after the results of the test). Almost 30% of the patients with primary polydipsia can be labeled as central diabetes insipidus even after this test. While this age-old method is still standard test, its interpretation is difficult when one wants to differentiate central DI from primary polydipsia due to two reasons: any water diuresis may compromise the renal medullary concentration gradient and promote a down-regulation of kidney aquaporin-2 water channels, which could potentially affect reading values of urinary osmolality measurements.

In this prospective, multi-center study, authors evaluated the diagnostic utility of Copeptin -based approach (copeptin is a degradation product of ADH and is much easier to measure reliably as compared to ADH), in differentiating central DI from primary polydipsia. Direct measurement of Copeptin after administration of hypertonic saline (250 ml bolus followed by 0.15ml/kg/hr infusion targeting serum Na of at least 150), showed significantly improved diagnostic accuracy over water deprivation test (96.5% vs 76.6%, P<0.001).Water deprivation one of that cruel and risky thing that doctors do to their patients (only another comparison I can imagine is the unscientific ritual of clamping urinary catheters in patients on diuretics!) Hoping to get copeptin measurements available, so that nephrologists who are well versed with using hypertonic saline (your turn to get teased by endocrinologists now!) can increasingly evaluate  patients with polyuria.

 

3) BP threshold to initiate therapy in elderly

Most Indian television daily soaps feature the nauseating age-old “saas-bahu’ (mother in law-daughter in-law) drama. Directors of these serials usually have IQ that competes with room temperature but we must acknowledge their unique skill:  both wife and mother can identify themselves as the victim of the situation (who in fact is a third person called ‘the husband’- regularly getting in trouble in such situations). But happy husbands are those who can hear both the sides carefully and listen to none.

Annals of Int Med features ‘Beyond the guidelines’ where they discuss a case of elderly hypertensive Mr. L who is in similar dilemma-identifying right BP threshold that will benefit him most and harm least in the light of conflicting guidelines by “saas-bahu ”- ACC/AHA vs ACP (you can choose to assign ‘saas or bahu’ status as per your discretion; a sorry situation! No choice here).

Husbands here are those smart physicians who can read them both and listen to no one but the interests of the patient sitting in front of them.

This is a worth reading piece for those who care about patients more than guidelines and individualize BP threshold to best suit patient’s need.

While some of us can afford to debate the debatable, here is what I like the most about blood pressure research-extensive over intensive approach. In a multicenter trial involving 700 patients from Sri Lanka, fixed low-dose triple-drug-combination was more likely to achieve BP control than the conventional approach (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Although limited by short follow up and pragmatic nature, results shown are encouraging especially in developing countries where BP treatment is far from optimum due to various barriers like complex drug supply chain, limited access to medications, and the shortage of healthcare workers to titrate medications.

4) Technique failure in the first year after PD initiation 

Whether it occurs in the first year or later, ‘technique failure’ is a catastrophe for a patient who chooses PD as a modality of dialysis. This is more likely early after initiation, and authors of this AJKD study evaluated data from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) Study, involving 16,748 patients included in the study, 4,389 developed early technique failure. Age >70 years, diabetes or vascular disease, prior renal replacement therapy, late referral to a nephrology service, or management in a smaller center were associated with higher risk of technique failure while Asian or other race and use of continuous ambulatory PD were associated with reduced risk, as was initiation of PD therapy in 2010 through 2014.

Admitting the retrospective nature and possible residual confounding, this data represents the largest evaluation of early technique failure using the recommended definition of this complication (which remains the major limitation of the previous studies).

I disagree with the preamble of this article that goes like this, “concerns regarding technique failure is a major barrier to increased uptake of peritoneal dialysis”. In many parts of the world, the major barrier may be the skewed incentive structure of HD vs PD. This leads to the selection of patients who have exhausted all the access options for HD (this is the most common reason why the patient chooses PD as last resort and comes for catheter implantation at our center)

 

5) Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy

In a prospective study in a Mesoamerican nephropathy hotspot in Nicaragua, Kupferman et al observed that a substantial fraction of sugarcane workers, who had no clinical evidence of kidney disease before the harvest season, developed AKI during the harvest season. Follow-up of the workers with AKI revealed that as a group, these workers had a partial recovery of kidney function.

Of the 326 sugarcane workers with normal preharvest serum creatinine values and no history of CKD, 34 (10%) had AKI (rise in creatinine >0.3 mg/dL). Of 34 workers with AKI, 29 participated in the first follow-up about 6 months later. 10 of 29 (34.5%) workers had eGFRs <60 mL/min/1.73 m2 and 11 of 29 (37.9%) developed an eGFR decrease > 30% by the time of their last follow-up. Working as a cane cutter (compared to working as a seed cutter, weeder, pesticide applicator, or irrigator) was associated with a 20% higher creatinine level.

AKI burden in this population is likely to be underestimated. Recurrent episodes of even minor renal injury may add up and lead to chronic tubulointerstitial damage. The fact that most of the AKI occurred in cane cutters indicates that strenuous work probably contributes to the injury. Hypothesis-generating studies like this would go a long way to help devise a preventive strategy at the community level.

 

6) Consumerism, Innovation, and the Future of Pediatric Primary Care

Alexander G. Fiks and colleagues wrote an opinion piece in JAMA Pediatrics to highlight the limitations of the healthcare model from the point of view of the families who avail pediatric primary care in its current form in the USA. They cite the example of Blockbuster, an US-based provider of home movie and video game rental services going bankrupt failing to see the changing needs of its consumers, as opposed to Netflix,  who now has more than 100 million subscribers, achieved dominance by betting on emerging technology for streaming video.

Creative destruction, what happened to Blockbuster, is driven by changes in technology and consumer priorities. Healthcare systems could learn a lot from this example.

Almost all the current healthcare systems deliver expensive services through inflexible infrastructure. These systems are often inefficient and have high fixed costs. Nephrology is not an exception. We could do a much better job if we identify how our patients’ needs are changing.

Much of the nephrology research is about fixing numbers- how to lower phosphate, how to keep PTH in the range, how to jack up the Kt/V, and for that matter, years on dialysis. We are in search of a renal troponin for a long time. Home dialysis and palliative care are ignored right from the training years. It’s time we wake up as a community and align our priorities with those of our patients and their families.

 

7) When the color of peritoneal dialysis effluent can be used as a diagnostic tool

What do you do when your PD patient comes to the clinic with an effluent bag that is red, orange, cloudy, milky white, green, yellow, purple or black? A lucid review article in Seminars in Dialysis by Thomas Dossin and Eric Goffin is a must-read. Authors describe various causes of discoloration of PD fluid. They briefly discuss investigations and management issues in such cases. I must admit I did not know nifedipine could cause chyloperitoneum in PD patients!