Thursday, November 21, 2013

Monday, November 18, 2013

Thursday, November 14, 2013


Another nail in the coffin for combination ACE/ARB in diabetic nephropathy!

Also see Kiran/Pradeep's posts on this article on Nov 10th.
Regarding Pradeep's question: might there still be a role for combined ACE/ARB in non-diabetics with CKD and proteinuria?  Obviously this study was in diabetics and will not directly inform ACE+ARB use in non-diabetics. But its impressive that their findings generally confirm those in ONTARGET, suggesting adverse outcomes (renal failure, hyperkalemia) with combination therapy.  ONTARGET included both diabetics and non-diabetics, and subgroup analysis suggested the adverse outcomes were not affected by the presence/absence of diabetes.

So I will continue to consider combined ACE/ARB only in very exceptional circumstances (perhaps multi-drug resistant hypertension and/or severe refractory proteinuria), and only with diligent laboratory monitoring.

Sunday, November 10, 2013

Demystifying kidney disease for the average Joe!: Can certain herbal medications treat chronic kidne...

Demystifying kidney disease for the average Joe!: Can certain herbal medications treat chronic kidne...: I set off to try and answer this question after one of my patients whom I saw at my Bradenton clinic brought along an article that claimed ...

Nice one on "NETTLE". I had one recently who asked me about Nettle.

Precious Bodily Fluids: Tolvaptan, ADPKD, and lack of vision at the FDA

Precious Bodily Fluids: Tolvaptan, ADPKD, and lack of vision at the FDA: About a year ago the ASN Kidney Week hosted the most exciting Late Breaking Trial Session I have attended. The session included the first pu...

Abatacept in B7-1–Positive Proteinuric Kidney Disease — NEJM

Abatacept in B7-1–Positive Proteinuric Kidney Disease — NEJM

A New Era of Podocyte-Targeted Therapy for Proteinuric Kidney Disease — NEJM

A New Era of Podocyte-Targeted Therapy for Proteinuric Kidney Disease — NEJM

Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy — NEJM

Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy — NEJM

APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease — NEJM

APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease — NEJM

New Therapies for Diabetic Kidney Disease — NEJM

New Therapies for Diabetic Kidney Disease — NEJM

The End of Dual Therapy with Renin–Angiotensin–Aldosterone System Blockade? — NEJM

The End of Dual Therapy with Renin–Angiotensin–Aldosterone System Blockade? — NEJM

Thursday, October 3, 2013

Uremic Pericarditis — NEJM

Uremic Pericarditis — NEJM
TMA (Thrombotic Microangiopathy) Classification:

1) TMA associated with genetic/immune mediated abnormalities.
2) TTP associated with genetic or immune mediated ADAMTS 13 abormalities
3) Infectious Disease associated TMA (e.g. STEC-HUS, HIV)
4) Systemic Disease associated TMA ( e.g APLA, SLE, Malignant HTN, malignancy etc)
5) Pregnancy associated TMA (TTP, HELLP, post partum HUS)
6) Drug associated TMA ( CNI, clopidogrel, Anti-VEGF)
7) Transplant associated TMA.

Reference : Schmidtko J et al atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab. Am J Kidney Dis. 2013 Feb

Nephron Power: Consult Rounds: Why does infusion of normal saline cause metabolic acidosis?

Nephron Power: Consult Rounds: Why does infusion of normal saline cause metabolic acidosis?

Tuesday, May 21, 2013

Renal Fellow Network: Does she drink tea?

Renal Fellow Network: Does she drink tea?: I was quickly moving along through my busy university clinic, seeing another CKD patient when the nurse came to inform me that the patien...

Wednesday, May 1, 2013

41 yo women 30 weeks pregnant (IVF twins) admitted to labor and delivery for possible preterm labor.  She has a history of liver transplant 20 years ago for "autoimmune hepatitis" managed with tacrolimus; levels throughout pregnancy have been 3-5.  She has had a mild transaminitis for the last several months (AST/ALT in the 125-200 range), mild hyperbilirubinemia (TB 2.5), mild hypoalbuminemia (alb 3.0), and normal INR.  She has had chronic intermittent nausea/vomiting throughout pregnancy.  In addition to prograf, her outpatient medication regimen includes lasix 40mg daily, which she has been on for "years" and has been continued during pregnancy.

On evaluation in labor and delivery, she is normotensive (105/75), with 1+ bilateral lower extremity edema.  Over the next 36 hours, her renal function progressively declines: Cr 1.0 on admission, up to 1.3 then - despite 100ml/h normal saline for 8 hours - 1.6 mg/dl.  No new meds, no contrast exposure, no NSAIDs.  Prograf level 5 days ago was 5.0, and dosage was increased from 1.5mg bid to 2 mg bid.  Repeat prograf level is pending.  Ob/gyn says she is not in labor, and the fetuses are appropriate for gestational age.

Any ideas?

Tuesday, April 16, 2013

Hypomagnesemia due to proton pump inhibitor

Last week I saw a patient on the consult service with severe hypomagesemia (Mg 0.6). Not on any diuretics, no diarrhea... but chronically on pantoprazole. 

I found this editorial in this month's KI, which gives a good review of Mg handling and the proposed mechanism of the PPI effect.  Some "pearls" from this editorial regarding PPIs and the kidneys:
  • Renal issues with PPIs include allergic interstitial nephritis, interference with calcinurin inhibitor metabolism, hyponatermia (rare), and most recently, hypomagnesemia
  • The mechanism of hypomagnesemia appears to be inhibition of active Mg absorption by the gut, likely due to increased gut luminal pH.
  • Risk factors for hypomagnesemia due to PPIs include advanced age, longstanding PPI use (years), and concomitant diuretic use
  • Treatment = discontinuation of the PPI, or if this is not advisable, oral magnesium replacement and discontinuation of any diuretics (to minimize renal Mg wasting).

Saturday, March 30, 2013

Core Curriculum in Nephrology

The AJKD has published a "Core Curriculum in Nephrology" which is a (near)-comprehensive tabulation of the medical knowledge of Nephrology.  A good resource for board review, the articles are freely available on the UPenn Renal Division website.  Many other landmark articles can be found there as well.  Thanks Dr Kopyt for bringing this useful site to my attention.

Friday, March 29, 2013

Rosuvastatin may prevent contrast nephropathy

In a study presented at the American College of Cardiology conference last month (PRATO-ACS), rosuvastatin significantly reduced the risk of contrast-induced nephropathy in the setting of NSTEMI.  Statin-naive patients with NSTEMI were randomized to receive rosuvastatin (40mg on admission then 20mg daily indefinitely) or atorvastatin only after discharge.  Patients in the rosuvastatin group had a lower incidence of CIN (6.7% vs 15.1%), defined as 25% or 0.5mg/dl increase in serum creatinine within 72 hours of contrast exposure.  Rosuvastatin is non-formulary at LVHN, but it seems likely to be a class effect so other statins could probably be substituted.

Thanks to Henry Schairer for calling my attention to this study.

Tuesday, March 26, 2013

Renal Fellow Network: Skin Lesions in Dialysis - Part 2

Renal Fellow Network: Skin Lesions in Dialysis - Part 2: Phototoxic skin disorders in renal failure: Patients with renal failure or ESRD secondary SLE can have a photosensitive skin rash. ...

Wednesday, March 20, 2013

Renal Fellow Network: Skin Lesions in Dialysis Patients - Part 1

Renal Fellow Network: Skin Lesions in Dialysis Patients - Part 1: Nephrology grand rounds in Duke University Medical Center this week inspired me to write this blog on a subject I now realise that I am...

Tuesday, March 12, 2013

Renal Fellow Network: Pathology Case of the Month

Renal Fellow Network: Pathology Case of the Month: An elderly woman presented for evaluation to the rheumatology service with arthritis and neuropathy. She was hypertensive and had microscop...

Tuesday, February 26, 2013

Thursday, February 21, 2013

AKI from valacyclovir?

Today in fellows clinic we saw an octogenarian with acute renal failure of unclear etiology.  She has CLL (in remission) and is on valacyclovir for chronic, recurrent HSV.  The question arose of whether valacyclovir is associated with acute kidney injury.

I happened upon this study which came out in AJKD last month.  Contrary to conventional wisdom, acyclovir and valacyclovir do not appear to be associated with AKI hospitalizations, at least within 30 days of new Rx, and as compared with famciclovir.

Sunday, February 17, 2013

Elevated Total Serum Calcium with normal Ionized Calcium.

Happens in multiple myeloma. Treatment not indicated.

Friday, February 15, 2013

Case 4-2013 — NEJM

Case 4-2013 — NEJM

Answer and full case discussion of renal infarct case published in NEJM few weeks back.

Thursday, February 14, 2013

Tuesday, February 12, 2013

Dialysis Modality and Correction of Uremic Metabolic Acidosis: Relationship with All-Cause and Cause-Specific Mortality

Monday, February 11, 2013


1) Can Ocular NSAIDS (e.g ketorolac eye drops) cause AKI?

2) Can Topical NSAIDS (e.g diclofenac skin cream) cause AKI ?  

Thursday, February 7, 2013

Wednesday, February 6, 2013

In Renal Rounds today Dr. Ali presented a case of 78 year old white female with ARF and Nephrotic syndrome with negative serologies and Biopsy showed Minimal change disease. She had history of intermittent NSAIDs use. Dr. S. Verma mentioned that in most of adult MCD with ARF, biopsies also show ATN, which is supported by the following paper.

Attached is retrospective study (cJASN) from columbia and NIH group.  Other important points from this article:

1.MCD with ARF, patients tend to be older and hypertensive with lower serum albumin and more proteinuria than those without ARF.
2.At follow up, patients with an episode of ARF had higher serum creatinine than those without ARF. 3.These patients were less likely to have responded to steroids and more likely to have FSGS on repeat renal biopsy

Tuesday, February 5, 2013

In today's board review with Dr. Reichart, we had a question on Fabry Disease. Attached are two articles.

Imp points: 

X-linked recessive lysosomal storage disease caused by deficient activity of the lysosomal enzyme alpha galactosidase A.

Biopsy of involved or uninvolved skin is relatively non invasive way of making diagnosis.
Presence of Oval fat bodies and lipid droplets with a lamellar pattern and Maltese cross pattern under polarized microscopy of urinary sediment.

Urinary excretion of globotriaosylceramide (Gb3), also known as ceramide trihexoside (CTH), is another
useful approach to diagnosing.

On EM- Enlarged secondary lysosomes (myeloid or Zebra bodies) packed with lamellated membrane structures . These inclusions can vary in appearance, from granular to lamellated, the latter being more diagnostic.

25-50% patients progress to ESRD. Progression from CKD to ESRD  not affected by patient age at onset of CKD or magnitude of proteinuria.

Therapy with alpha-Gal A is associated with improved glomerular architecture and/or reduced glycolipid
deposits in the kidney, possible improvement in renal function.

Wednesday, January 30, 2013

New-Onset Diabetes after Transplant (NODAT)

The estimated rates at 12 months posttransplant are 20–50% for kidney transplants, 9–21% for liver transplants, and approximately 20% for lung transplants. NODAT is associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Besides the traditional risk factors for type 2 diabetes (age, family history, obesity, and ethnicity), exposure to immunosuppressive agents often precedes the occurrence of NODAT.

Below are some articles related to NODAT :

Renal Fellow Network: Pearls for Boards

Renal Fellow Network: Pearls for Boards: 1) Surreptitious vomiting or diuretic abuse - metabolic alkalosis, Laxative abuse - non-gap metabolic acidosis . 2)   Aquaporin 2 -  a...

Monday, January 28, 2013

I recently treated the below patient and would like to ask your opinion:

61 year old caucasian male with long standing diabetes-2 on insulin with baseline creatinine of 1.2-1.5 presented with left lower extremity swelling and fever. No h/o diabetic retinopathy. PMH includes CAD s/p CABG, charcots foot with recurrent right lower extremity cellulitis leading to right BKA. Creatinine at the time of this admission was 3.4. Has MRSA bacteremia and left lower extremity osteomyelitis of foot. Treated with daptomycin initially and then changed to lenezolid. Initial evaluation revealed 0.6 grms of proteinuria. Over a period of few days creatinine improved to 1.6. But started to worsen again gradually over next 10 days with peak creatinine of 3.8 and BUN 116. Developed fluid retention leading to pulmonary edema. Has worsening leukocytosis. He was started on Hemodialysis via right IJ tunnelled catheter.

1) What would be the cause of his recurrent AKI?
2) Would you do biopsy?
3) Any other investigations?

Friday, January 25, 2013


27 year old obese lady with CKD 3 with stable creatinine of 1.7 and 1 gm of proteinuria referred to you for opinion regarding her pregnancy.   Her etiology of CKD is FSGS thought to be secondary to obesity.  This is her first pregnancy and She is in her first trimester of pregnancy. She was adviced not to plan pregnancy because of CKD and also because of ARBs(Angiotensin Receptor Blockers). Inspite of the caution she conceived. Her BP is well controlled and physical exam is unremarkable except obesity. What would be your recommendation?

1) Terminate pregnancy.
2) Continue pregnancy as well as ARBs
3) Explain the risks and leave upto the patient to decide.
4) Continue pregnancy but change ARBs to methydopa.

Renal Fellow Network: eJournal Club - Hemodiafiltration

Renal Fellow Network: eJournal Club - Hemodiafiltration: A few years ago, a unit that I worked at started using hemodiafiltration (HDF) routinely for the first time. Prior to starting our patients...

Wednesday, January 23, 2013

Membranous Nephropathy: Treatment in setting of declining renal function

Roughly 1/3rd of patients with membranous nephropathy experience a progressive deterioration in renal function over time.  Thanks to Pradeep for bringing a new RCT from Lancet to our attention, which focuses on this subpopulation of MN with declining renal function.  This trial randomized patients to conservative treatment, cyclosporine x 12 months, or alternating montly chlorabucil/prednisolone.  Patients in the chlorambucil/prednisolone group had a lower risk (hazard ratio 0.44 [0.7-1.95]) of reaching the primary endpoint of a 20% further decline in renal function, as compared to the other two groups.  Notably, the chlorambucil group, but not the cyclosporine group, received steroids. The authors concluded "For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function, 6 months’ therapy with prednisolone and chlorambucil is the treatment approach best supported by our
evidence. Ciclosporin should be avoided in this subset."

Kiran Goli adds: The original ponticelli protocol still holds good and has a very good response rate. Chlorambucil was originally used in the study but most of the physicians use cyclophosphamide since studies revealed similar efficacy with less toxicity (most worrisome is malignancy). Some may choose CNI particularly in young patients with unfinished families for whom fertiility is important...Kiran.

Thursday, January 17, 2013

Loin Pain Hematuria Syndrome

54 year old female presented with 5 month history of B/L flank pain constant with intermttent exacerbations and one UA in past positive for blood, dipstick in office also positive for blood. No evidence of UTI. NSAIDs use on and off. One differential is LPHS.
Attached is a good review article .

Imp points: 
1.Majority of the cases are females but recent reports have higher male population. 
2.Pain episodes may be associated with low-grade fevers and dysuria, although there is no evidence of concurrent urinary tract infection.
3. Lowgrade proteinuria has been reported in some patients, primarily in the setting of an attack of flank pain.
4. Biopsy may show mild tubular atrophy, patchy interstitial fibrosis, glomerulosclerosis, arteriolar hyalinosis, and subcapsular cortical ischemia. Electron microscopy in some patients reveals abnormally thin or thick glomerular basement membranes.
5.In LPHS associated with Thin Basement membrane ACEIs can decrease severity of pain as suggested in this study. 

6.Most importantly, renal biopsy should be considered on all patients in whom the diagnosis of LPHS is considered as 21% patient were found to have immunoglobulin A nephropathy, especially if proteinuria (even tubular proteinuria) or renal dysfunction is present

Tuesday, January 15, 2013

Metformin-associated lactic acidosis

Today we saw a patient in continuity clinic for hospital follow-up who had been hospitalized with severe lactic acidosis (initial pH <6.8, lactate 14.7), shock, and severe acute renal failure. Her medications at the time of admission included metformin. No other cause of the lactic acidosis/shock was found (all cultures negative). She had longstanding DM and HTN, but no history of CKD. She was dialyzed once, and recovered fully.

Metformin-induced metabolic acidosis is a rare but well-characterized complication of metformin therapy, seen in the setting of either acute kidney injury or chronic kidney disease. Metformin is excreted by the kidneys, hence accumulates to toxic levels in the setting of acute or chronic kidney disease, either with chronic use or in acute overdose. Mortality in this condition is high (45%), and lactate levels are not predictive of mortaility. Metformin is thought to induce lactic acidosis via its inhibition of hepatic gluconeogenesis (conversion of lactate and pyruvate to glucose) and via a direct stimulation of lactate production from glucose in the small intestine. Hemodialysis should be considered in the setting of metformin toxicity, especially when renal failure is present.

It should be noted that when used appropriately, large epidemiologic studies have failed to show an increased risk of metabolic acidosis in patients treated with metformin as compared with other diabetic medications, hence it is considered safe.

-SEM 1/11/13
This was a educational case, I found a good review article 
According to FDA prescribing guidelines Metformin is contraindicated for SCr >/=1.4 (women) and >/=1.5 (men) but with these SCr values there can be great variation in eGFR. Canadian, UK and Australian guidelines includes eGFR in addition or in place of SCr values and probably will be better to follow to prevent the use of metformin in people with low renal functions.
Higher metformin concentrations do not consistently occur in those with more severe degrees of lactic acidosis. Metformin levels are not linked to mortality in those who develop lactic acidosis, perhaps reflecting the primary effect of the underlying cause of the acidosis (e.g., hypoxia, hemodynamic compromise) on outcomes rather than incriminating metformin itself. Even with these limitations I think MALA should be a differential and as Dr. Maynard mentioned IHD/CRRT should be considered, especially in patients with renal failure.
Pradeep 1/12/13