Diabetic Nephropathy, or not?

A man in his 30s with a history of type 1 DM and chronic hypokalemia was referred to the renal clinic for investigation of CKD. His creatinine was 1.8g mg/dl.  His DM was well controlled without any evidence of retinopathy.  Urinalysis did not show any proteinuria or hematuria.  His renal biopsy showed focal tubular atrophy, dystrophic calcification in the scattered tubules, and did not have any signs of diabetic nephropathy.  His renal biopsy findings were therefore attributed to chronic hypokalemia.

Hypokalemia can cause kidney damage if it persists for longer than one month.   Chronic hypokalemia can cause non-specific vacuolar lesions in the epithelial vessels in the proximal tubules.  Typical renal biopsy will show interstitial nephritis, fibrosis, tubular atrophy and cyst formation.  The pathogenesis of hypokalemic nephropathy is not clear.  The hypotheses are:  1) complement activation and tubular cell damage by hypokalemia induced renal ammonium production 2) stimulation of cell growth and proliferation by intracellular acidosis 3) increased production of growth factors (VEGF, IGF-1) and cytokines by hypokalemia through an uncertain mechanism.

After further work-up, our patient was diagnosed with Giltelman syndrome.  He was started on potassium replacement and his Cr has remained stable since then.  

Posted by Jie Cui

Pregnancy and Dialysis

A woman with no past medical history was admitted to the ICU service with acute kidney injury secondary to atypical HUS. She was early in pregnancy and we were consulted in order to start dialysis. The management of a pregnant dialysis patient is no simple matter.

About 13-36% of TTP-HUS in women is associated with pregnancy. Pregnancy may be a risk factor for developing TTP-HUS because of hypercoagulability, loss of integral endothelial cell membrane proteins, decreased fibrinolytic activity and ADAMTS13 activity. Among all patients with pregnancy associated TTP-HUS, 8% occurs in the 1^st trimester, 16% in the 2^nd trimester and 77% in the 3^rd trimester or post-partum. 

There are a number of factors to think about in the management of pregnant dialysis patients:

1. Duration and frequency of dialysis:  Pregnant patient usually start on daily dialysis with a predialysis BUN goal of <50mg/dl. It has been shown that patients on nocturnal hemodialysis with an average of 48hours/week have better outcomes than women who dialyzed 20 to 26 hours/week.

2. Anemia:  Pregnant women usually require higher doses of erythropoietin and iron, with goal of Hg>10g/dl, and transferrin saturation>30%. These targets are based more on patients in the general dialysis population and are not evidence based. Pregnant women are usually anemic although their red cell mass increases.

3. Hypophosphatemia: Our daily phosphorous ingestion is 800 to 1600mg. 2.5g to 3.0g phosphorous is removed during a regular 4 hour dialysis treatment. Phosphorous levels will decrease in patients who receive intensive hemodialysis.   Hypophosphatemia can cause tissue hypoxia and intracellular depletion of adenosine triphosphate with impairment of glucose metabolism. In a pregnant patient, our goal is to keep the phosphorous level >3mg/dl with either po repletion or supplemental phosphorous in the dialysate.

4. Calcium: 25 to 30 g of calcium is required for fetal skeletal growth. This demand requires transfer of 140mg/kg/day calcium across the placenta. To prevent osteopenia, it is recommended that an additional 1500mg of calcium be ingested daily during pregnancy.

In conclusion, adequate dialyses, treatment of anemia, maintenance of nutrition and electrolyte stability are the most important factors for a successful pregnancy in chronic dialysis patients. The outcomes of pregnancy in dialysis patients were reviewed in a previous blog post.

 

Our patient was started on 6 times/week hemodialysis for 4 hours each session.  Her phosphorous level was 2-2.5mg/dl after 1 week on hemodialysis.  With aggressive oral repletion and a regular diet, her phosphorous level was maintained at 3mg/dl upon discharge. 

Posted by Jie Cui

Beads on a String

A 41 year old gentleman with no past medical history presented to ER for nausea, vomiting and abdominal pain. Abdominal CT showed bilateral renal infarcts. His labs were notable for a Cr of 1.4, LDH 500 ESR 102.

The commonest causes of renal infarcts are emboli from atrial fibrillation, infective endocarditis, or fat, renal artery or aortic dissection, fibromuscular dysplasia and vasculitis. Work-up including an EKG, ECHO, hypercoagulable panel and antiphospholipid antibodies were all negative. We performed an angiogram which showed diffuse visceral microaneurysms leading to a diagnosis of polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that affects medium sized vessels. It was first described by Dr. Kussmaul and Dr. Maier in 1866. The incidence of the disease is 2 to 33 per million population, with a male to female ratio of 1.5:1. The major environment factor associated with PAN is HBV infection.

There are 5 variables that predict an increased risk of mortality in PAN (Five factors score FSS): 1) Proteinuria>1g/day

2) Renal insufficiency (Cr>1.58)

3) GI involvement (bleeding perforation, infarction or pancreatitis)

4) Cardiomyopathy

5) Central venous system involvement.

Without treatment, the 5 year mortality in patients with 0 risk factor is <12%, 1 risk factor 25% and 2 risk factors 56%. The standard treatment for FSS>1 is 12 months Cytoxan with steroids. Renal failure is rare in PAN patients and uncontrolled or relapsing vasculitis is the most common cause of death.

In our case, the patient was started on cytoxan and prednisone and his abdominal pain completely resolved. His creatinine unfortunately is still elevated and the plan is to continue with treatment for at least 6 months.

Posted by Jie Cui