Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Short answer: often not! This is because most studies have shown frequently high ESR’s in stable “uninflamed” patients with chronic renal failure (CRF) (including those on dialysis) at levels often associated with infection, connective tissue disease, or malignancy. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevated ESR (greater than 60 mm/h), with 20% having ESR greater than 100 mm/h; type or duration of dialysis had no significant effect on ESR levels.1 Another study reported a specificity for abnormal ESR of only 35% for commonly considered inflammatory conditions (eg, infections or malignancy) among patients with CRF. 2

But is it the chronic inflammation in diseased kidneys or the uremic environment that elevates ESR? A cool study compared ESR in CRF in patients who had undergone bilateral nephrectomies with those with retained kidneys and found no significant difference in the ESR between the 2 groups. 4  So it looks like it’s the uremic environment, not diseased kidneys themselves that result in elevated ESR in these patients.

The mechanism behind these observations seem to reside entirely within the patients’ plasma, not the erythrocytes. Within the plasma, fibrinogen (not gammaglobulins) seem to be the most likely factor explaining elevated ESR among patients with CRF. 1,2

Bonus pearl:  Did you know that ESR is nearly 100 years old, first described in 1921? 5


  1. Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40.
  2. Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801.
  3. Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224.
  4. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248.
  5. Fahraeus R. The suspension stability of the blood. Acta Med Scan 1921;55:70-92.


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Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Could constipation contribute to hyperkalemia in my patient with chronic kidney disease?

Yes! Constipation may be an important contributor to hyperkalemia in some patients with chronic kidney disease (CKD).

 Under normal conditions, 80-90% of excess dietary potassium (K+) is excreted by the kidneys, with the remainder excreted through the GI tract.1 However, in advanced CKD, particularly in the setting of end-stage kidney disease (ESKD), the GI tract assumes a much more important role in maintaining K+ balance. 

As early as 1960’s, the daily fecal excretion of K+ was found to be directly related to the wet stool weight, irrespective of creatinine clearance. Furthermore, K+ excretion in stool was as high as ~80% of dietary intake (average 37%) in some hemodialysis (HD) patients compared to normal controls (average 12%). 2

Such increase in K+ excretion in the GI tract of patients with CKD was later found to be primarily the result of K+ secretion into the colon/rectum rather than reduced dietary K+ absorption in the small intestine 1,3, was inversely related to residual kidney function, and as a consequence could serve as the main route of K+ excretion in patients with ESKD. 4

Collectively, these findings suggest that in addition to non-dietary factors such as medications, we may need to routinely consider constipation as a potential cause of hyperkalemia in patients with advanced CKD or ESKD. 1

Bonus Pearl: Did you know that secretion of K+ by the apical surface of colonic epithelial is mediated in part by aldosterone-dependent mechanisms? 5


  1. St-Jules DE, Goldfarb DS, Sevick MA. Nutrient non-equivalence: does restricting high-potassium plant foods help to prevent hyperkalemia in hemodialysis patients? J Ren. Nutr 2016;26: 282-87.
  2. Hayes CP, McLeod ME, Robinson RR. An extrarenal mechanism for the maintenance of potassium balance in severe chronic renal failure. Trans Assoc Am Physicians 1967;80:207-16.
  3. Martin RS, Panese S, Virginillo M, et al. Increased secretion of potassium in the rectum of humans with chronic renal failure. Am J Kidney Dis 1986;8:105-10.
  4. Cupisti A, Kovesdy CP, D’Alessandro C, et al. Dietary approach to recurrent or chronic hyperkalemia in patients with decreased kidney function. Nutrients 2018, 10, 261;doi:10.3390/nu10030261.
  5. Battle D, Boobes K, Manjee KG. The colon as the potassium target: entering the colonic age of hyperkalemia treatment. EBioMedicine 2015;2: 1562-1563.


Contributed in part by Alex Blair, MD, Mass General Hospital, Boston, MA.

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Could constipation contribute to hyperkalemia in my patient with chronic kidney disease?

What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?

Terry’s nails were first described in 1954 in patients with hepatic cirrhosis (prevalence 82%, majority related to alcohol abuse) (1). Since then, they have been reported in a variety of other conditions, including adult-onset diabetes mellitus (AODM), chronic congestive heart failure, chronic renal failure, pulmonary tuberculosis, and Reiter’s syndrome (2).

A 1984 study found Terry’s nails in 25% of hospitalized patients (3).  In this study, cirrhosis, chronic congestive heart failure, and AODM were significantly associated with Terry’s nails, while pulmonary tuberculosis, rheumatoid arthritis and cancer were not. The presence of Terry’s nails may be particularly concerning in patients 50 y of age or younger as it increases the relative risk of cirrhosis, chronic congestive heart failure or AODM by 5-fold (18-fold for cirrhosis alone) in this age group (3).

Terry’s nails should be distinguished from Lindsay’s nails or “half and half” nails. Although both nail abnormalities are characterized by an opaque white proximal portion, Terry’s nails have a thinner distal pink to brown transverse band no more than 3 mm wide (3) (Fig 1), while the same anomaly is wider and occupies 20%-60% of the nail bed in Lindsay’s nails (Fig 2). Of interest, Lindsay’s nails have been reported in up to 40% of patients with chronic kidney disease (4,5).


1. Terry R. White nails in hepatic cirrhosis. Lancet 1954;266:757-59. 
2. Nia AM, Ederer S, Dahlem K, et al. Terry’s nails: a window to systemic diseases. Am J Med 2011;124:603-604. 
3. Holzberg M, Walker HK. Terry’s nails: revised definitions and new correlations. Lancet 1984;1(8382):896-99. 
4. Pitukweerakul S, Pilla S. Terry’s nails and Lindsay’s nails: Two nail abnormalities in chronic systemic diseases. J Gen Intern Med 31;970. 
5. Gagnon AL, Desai T. Dermatological diseases in patients with chronic kidney disease 2013;2:104-109.

Figure 1. Terry’s nails in a patient with end-stage liver disease

Figure 2. Lindsay’s nails in a patient with chronic kidney disease

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What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?

Should Aerococcus urinae growth from the urine of my elderly patient be considered a pathogen?

Although for many years Aerococcus urinae was considered a urinary contaminant, increasingly it is recognized as an emerging pathogen capable of causing not only urinary tract infection (UTI) but also secondary bacteremia and endocarditis, among others.1   

The proportion of patients with aerococcal bacteriuria with symptoms suggestive of UTI ranges from 55-98%.1 So A. urinae can no longer be assumed to be a contaminant, particularly in the presence of symptoms suggestive of UTI.

A. urinae UTI often affects the elderly (median age 79 y) and those with pre-existing urinary tract pathologies, such as prostatic hyperplasia, urethral stricture, renal calculi, and prior urinary tract surgery.2,3 Many patients also have underlying comorbidities such as diabetes, heart disease, dementia, and chronic renal failure.3

One clue to the presence of A. urinae in the urine is its particularly pungent odor reminiscent of that of patients with trimethylaminuria (fish odor syndrome).4

Once you decide you should treat A. urinae, keep in mind that it is NOT predictably susceptible to trimethoprim-sulfamethoxazole, fluoroquinolones, or fosfomycin!  Instead, consider penicillin, ampicillin, cephalosporin, or nitrofurantoin to which most strains are susceptible.5,6.



  1. Rasmussen M. Aerococcus: an increasingly acknowledged human pathogen. Clin Microbiol Infect 2016;22:22-27.
  2. Tathireddy H, Settypalli S, Farrell JJ. A rare case of aerococcus urinae infective endocarditis. J Community Hosp Intern Med Perspectives 2017; 7:126-129.
  3. Higgins A, Garg T. Aerococcus urinae: An emerging cause of urinary tract infection in older adults with multimordidity and urologic cancer. Urology Case Reports 2017;24-25.
  4. Lenherr N, Berndt A, Ritz N, et al. Aerococcus urinae: a possible reason for malodorus urine in otherwise healthy children. Eur J Pediatr. 2014;173:1115-7
  5. Christensen JJ, Nielsen XC. Aerococcus urinae. Antimicrobe @ http://www.antimicrobe.orgb75.asp , accessed June 14, 2018.
  6. Dimitriadi D, Charitidou C, Pittaras T, et al. A case of urinary tract infection caused by Aerococcus urinae. J Bacteriol Mycol 2016; 2: 00041.


Should Aerococcus urinae growth from the urine of my elderly patient be considered a pathogen?

Should my patient with non-valvular atrial fibrillation on hemodialysis be anticoagulated?

Whether patients with end-stage kidney disease (ESKD) and non-valvular atrial fibrillation (AF) benefit from anticoagulation is a matter of controversy. 1,3 Although there may be some suggestion of benefit of warfarin for stroke prevention in this patient population, 2 there is also a higher concern for bleeding. 4-6 An increased risk of stroke among patients with ESKD and AF on warfarin has also been reported. 7

A 2018 Kidney Disease:Improving Global Outcomes (KDIGO) Controversies Conference concluded that there is “insufficient high-quality evidence” to recommend anticoagulation for prevention of stroke in patients with ESKD and atrial fibrillation. 8

However, the 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/ Heart Rhythm (HRS) guideline states that it is reasonable to consider warfarin therapy in patients with ESKD and non-valvular AF with CHA2DS2 -VASc score of 2 or greater (Class IIa recommendation, level of evidence B).8 Of interest, the FDA recently approved the use of a direct oral anticoagulant (DOAC), apixaban, in ESKD potentially providing an alternative to the use of warfarin when anticoagulation is considered.10

Perhaps the decision to anticoagulate patients with ESKD for atrial fibrillation is best made on a case-by-case basis taking into account a variety of factors, including the risk of thromboembolic event, the risk of bleeding complications as well as patient preference.


1. Genovesi S, Vincenti A, Rossi E, et al. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis 2008;51:255-62.

2. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012;367:625-35.

3. Shah M, Avgil TM, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation2014;129:1196-203.

4. Elliott MJ, Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis 2007;50:433-40.

5. Holden RM, Harman GJ, Wang M, Holland D, Day AG. Major bleeding in hemodialysis patients. Clin J Am Soc Nephrol 2008;3:105-10.

6. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010;77:1098-106.

7. Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol2009;20:2223-33.

8. Turakhia MP, Blankestijn PJ, Carrero J, et al. Chronic kidney disease and arrythias: conclusions from a Kidney Disease:Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J, ehy060. Published 07 March 2018.

9. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation 2014;130:2071-104. 

10. Moll S. Use of direct oral anticoagulants in patients on hemodialysis. Diffusion, October 11, 2017. 

Contributed by Brad Lander, MD, Mass General Hospital, Boston, MA.

Should my patient with non-valvular atrial fibrillation on hemodialysis be anticoagulated?

When should I consider bicarbonate (BC) replacement in my patient with renal insufficiency?

Metabolic acidosis is one of the earliest complications of chronic kidney disease (CKD), with a direct correlation between the decline in glomerular filtration rate (GFR) and reduction in serum BC1.

Epidemiologic studies in patients with CKD have reported an independent association between serum BC (<22 meq/L considered low) and adverse renal outcomes and mortality1. Limited data from small interventional trials of alkali therapy supplementation and dietary interventions (eg, increased fruit and vegetable intake) have shown the benefits of raising serum BC. Specifically, 1 study involving patients with CKD stages 4 and 5 and another involving CKD stage 2 hypertensive nephropathy reported slower decline in creatinine clearance/eGFR in patients receiving BC replacement2,3.  

Less is known on the potential benefit of BC replacement in patients with acute kidney injury (AKI) with a recent Cochrane review finding no randomized controlled trials4 and national guidelines not recommending either in favor or against its use AKI5. Of note, BC therapy has also been associated with sodium and fluid overload, an increase in lactate and PCO2, and a decrease in serum ionized calcium6.


  1. Dobre M, Rahman M, Hostetter TH. Current status of bicarbonate in CKD. J Am Soc Nephrol 2015;26:515-523.
  2. de Brito-Ashurst I, Varagunam M, Raftery MJ, et al. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 2009; 20: 2075–2084.
  3. Mahajan A, Simoni J, Sheather SJ, et al. Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. Kidney Int 2010;78: 303–309.
  4. Hewitt J, Uniacke M, Hansi NK, et al. Sodium bicarbonate supplements for treating acute kidney injury. Cochrane Database of Systematic Reviews 2012; Jun 13; (6):CD009204. doi: 10.1002/14651858.
  5. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 2013;61:649-72.
  6. Sabatini S, Kurtzman NA. Bicarbonate therapy in severe metabolic acidosis. J Am Soc Nephrol 2009;20:692-695.


Contributed in part by Cynthia Cooper, MD, Mass General Hospital, Boston, MA.

When should I consider bicarbonate (BC) replacement in my patient with renal insufficiency?