Arasu Gopinath, MD Nephrology Associates of Utah

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1 Arasu Gopinath, MD Nephrology Associates of Utah

2 Topics of interest PPI and CKD Diet soda consumption and risk of Incident ESRD Dietary red meat and kidney toxicity Chronic interstitial nephritis in agricultural communities

3 PPI and CKD Issue: Are PPIs safe from a kidney perspective?

4 PPI and CKD (Al-Aly et al)

5 PPI and CKD

6 PPI and CKD

7 PPI and CKD

8 PPI and CKD

9 PPI and CKD Common cause of AIN Previous case cohort studies from NZ and Ontario showed the AIN link Subtle without classic clinical findings of AIN (< 50% fever, < 10% rash, < 30% eosinophilia etc) Recognized late. Delayed diagnosis likely leads to CKD (30-70% of AIN did not fully recover renal function) Link to CKD remained even after controlling for AKI Recent ARIC (atherosclerosis risk in communities) study showed link between CKD and self-reported PPI use (Lazarus et al JAMA , 2016)

10 PPI and CKD take home points Likely common and under-recognized cause of AIN Strong associative data for increased risk of CKD, even when controlled for AIN CKD likely due to evolution into chronic interstitial nephritis Absolute risk likely < 10% Would limit PPI to clear cut indications and monitor periodically.

11 Diet soda and kidney disease Issue: Does soda consumption lead to/ or worsen kidney disease?

12 Diet soda consumption and risk of Incident ESRD Rebholz et al, Johns Hopkins CJASN 2016

13 Diet soda consumption and risk of Incident ESRD ARIC study Prospective cohort study 15,792 men and women, predominantly Black North Carolina, Mississippi, Minnesota and Maryland Followed from till Semiquantitative food freq questionnaire x 2, (87-89 and 93-95) Baseline: Age years, 55% F, 27% Black, 12% DM, 35% HTN, kidney function normal (baseline GFR 100) (adjusted for age, sex, race-center, education level, smoking status, physical activity, total caloric intake, egfr, BMI category, diabetes, systolic BP, and serum uric acid) 43% 1 glass/ week, 18% 1-4 glasses/ week, 25% 5-7 glasses/ week, 13% > 7 glasses / week There were 357 incident ESRD cases over the 23 years of follow up

14 Diet soda consumption and risk of Incident ESRD

15 Diet soda consumption and risk of Incident ESRD

16 Diet soda consumption and risk of Incident ESRD Potential mechanisms: 1. High phosphorus load may increase FGF 23 levels, which is independently linked to CKD progression. 2. High phosphorus load may increase dietary acid load 3. could be a proxy for poor diet quality (often consumed as a substitute for sugar-sweetened beverages). 4. diet soda associated with incident metabolic syndrome. 5. diet soda is known to alter intestinal microbiome

17 Diet soda and ESRD-take home points Dose-response relationship exists Might be due to high phosphorus load and alteration of intraspinal microbes More likely reflects poor lifestyle

18 A sip of soda

19 A sip of soda

20 Dietary red meat and kidney toxicity Issue: Is dietary red meat bad for the kidneys?

21 Dietary red meat and kidney toxicity ONTARGET data ONTARGET surprisingly suggested that increased animal protein consumption reduced the risk for incidence or progression of CKD!

22 Red meat intake and risk of ESRD

23 Red meat intake and risk of ESRD

24 Red meat intake and risk of ESRD

25 Red meat intake and risk of ESRD Substituting one serving of red meat

26 Red meat intake and risk of ESRD take home Possible explanations: High acid load take home Increased load of dietary advanced glycation end products (AGE) and advanced lipoxydation end products (ALE)

27 CINAC (chronic interstitial nephritis in agricultural communities)

28 CINAC central American nephropathy, Salvadoran agricultural nephropathy, Mesoamerican endemic nephropathy, CTID of Central America, Uddanam endemic nephropathy Worldwide, but predominantly tropical humid low altitude areas M: F 2.6:1 Present in stage 4-5 CKD, no proteinuria, metabolic alkalosis, with magnesium, phosphorus, sodium, potassium and calcium wasting small and scarred kidneys with irregular contour Bx: chronic tubulointerstitial nephritis (interstitial fibrosis/tubular atrophy with or without monocytic infiltration) EM: multi laminated myeloid structures in the proximal tubule, probably related to intracellular transport mechanism and degradation of substances by lysosomes. high cadmium levels Exposure to toxins in contaminated drinking water + heat stress with repeated episodes of dehydration + hyperosmolarity and hyperuricosuria (fructose mediated) (sugarcane juice consumption during work)

29 CKD checklist helps in better CKD care 12/1/

30 Update in Nephrology Thank you Arasu Gopinath, M.D.