Kidneys Inc.

medicine and nephrology updates and interesting cases by a practicing nephrologist in USA

Archive for the month “October, 2011”

Bilateral hydronephrosis with non-oliguric renal failure

93 y old man with PMH of prostate cancer successfully treated in another state lost to follow up for about 2 years, when he moved out of the state. Found to have elevated creatinine (increased from baseline of 1.5 4 months prior to 3.3 on presentation) on routine blood work with further investigation shooing b/l hydronephrosis on renal ultrasound. This asymptomatic patient with unknown duration of obstructive uropathy was admitted and no other obvious etiology was found for the worsening renal failure. Foley was inserted without difficulty, and patient was nonoliguric. Nephrostomy tubes were considered unnecessary. Patient discharged after initiating anti-androgen therapy for prostate cancer. Treatment started for prostate cancer with PSA trending down but no improvement in creatinine.

What would be the best next step?

1. Repeat US  to re-assess the b/l hydronephrosis

2. Reconsider decision for nephrostomy tubes

3. IV pyelogram to asses for ureteral obstruction and possible stents

4. Check viability and function with MRA

5. Check Viability with DMSA scan

6. None of the above

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Vitamin D : The sunshine vitamin

Being a nephrologist, I deal with bone disease related to chronic kidney disease on a daily basis and vitamin D is a major player in these patients. Also, I have been frequently asked about this by many people, so I thought it might be a good idea to put some relevant information together for a quick reference.

 

In June 2011, the endocrine society published recommendations for daily intake and optimum levels, based on extensive literature review. However, these are not based on

large randomized controlled trials (which haven’t been conducted, so far)

 

With whatever evidence we have, these are the take home points:

Main source for Vit D is diet, but very little present, except for oily fish. Another important source is UVB radiation, which converts 7 dehydrocholesterol to pre-vitamin D3 and then D3

Plants have vit D2 more like a pre hormone than a vitamin.

 

Vit D (either 2 or 3) gets hydroxylated at the position 25 in the liver (cyp2r1 &  cyp27a1), stable and half life is 2 wks.

Then, hydroxylated at position 1 in the kidney cyp27b1 (also present in other tissues)

This is the active form of vitamin D.

 

Measurement:

When serum levels are measured the 25 hydroxy form is measured since it is more stable, concentration about 1000 times more than the 25 hydroxy form

The hydroxylation at position 1 depends on PTH (parathyroid hormone), FGF-23 (fibroblast growth factor-23), Calcium, Phosphorus

 

Recommended daily doses of Vit D:

 

Age upto one year: At least 400 IU/day

1 year and older:  at least 600 IU/day However, at least 1000 IU/day of vitamin D may be needed to raise the blood level of 25(OH)D consistently above 30 ng/mL

19 to 70 years: at least 600 IU/day

>70 years: at least 800 IU/day of vitamin D.

In adults (>19 yrs) at least 1500 to 2000 IU/day of supplemental vitamin D may be needed to keep 25(OH)D levels above 30 ng/mL.

Pregnant and lactating women need a minimum of 600 IU/day of vitamin D; 1500 IU/day may be needed to maintain blood levels of 25(OH)D higher than 30 ng/mL.

“Obese children and adults and children and adults on anticonvulsant medications, glucocorticoids, antifungals such as ketoconazole, and medications for AIDS need at least 2 to 3 times more vitamin D for their age group to satisfy their body’s vitamin D requirement,”

Tolerable upper limits of vitamin D, which “should not be exceeded without medical supervision,” include the following:

  • 1000 IU/day for infants aged up to 6 months,
  • 1500 IU/day for infants aged 6 months to 1 year old,
  • 2500 IU/day for children aged 1 to 3 years,
  • 3000 IU/day for children aged 4 to 8 years, and
  • 4000 IU/day for everyone older than 8 years.

Of note all recommendations are only for bone health. No recommendations for ‘purported’ benefits of Vit D (for cancer, cardiovascular health) since they are mostly association studies.

 

Exposure to sunlight:

In fair skinned people: 10 minutes in mid day sun with no sunscreen (when UV index is < 3) is enough to produce about 10000 units of Vit D. This holds good provided the clothing is minimal exposing about 50% of the body. which essentially comes down shorts and tank top

In darker skinned individuals: the time required may be more.

Also note: darker individuals have lower risk for than fair skinned for skin cancer, so they probably could expose themselves longer in order to get the benefits of the natural vitamin D

 

Sunscreen recommendations

 

New FDA rules regarding sunscreen:

 

Sunscreens will carry a broad spectrum label- to indicate that it covers both UVA & UVB radiations

The SPF indicates protection against UVB only which is responsible for sunburn, skin cancer, and vitamin d production in the skin with sun exposure

While UVB affects only the outer layer of the skin, UVA enters deeper layers, 30-40 times more prevalent than the UVB, and linked to tanning and skin aging and skin cancer as well

 

Now, the highest SPF products can claim is 50+ since value above that are not meaningful in terms of protection

 

They can carry labels claiming to prevent cancer, only if SPF is higher than 15

 

Water resistant sunscreens will have to undergo testing, and labels have to specify time of protection in minutes for swimming/sweating

Manufacturers have one year to comply with these rules

Idiopathic(primary) FSGS and suPAR(soluble urokinase Plasminogen Activator Receptor)

Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome that could be idiopathic(primary) or secondary(genetic, infectious like HIV & parvo B19, drug induced IFN-alpha, pamidronate, lithium, Reflux nephropathy, hyperfiltration, HTN, obesity, Sickle cell etc). Clinically, it manifests as proteinuria with patients being asymptomatic to nephrotic. Proteinuria is non selective. Other features are HTN, Hematuria. with normal serological tests & complement levels. FSGS accounts for up to 1/3 of idiopathic nephrotic syndrome in adults and is the most common cause of nephrotic syndrome in african americans. Left untreated it frequently progresses to ESRD (End stage Renal disease.

While the management of secondary FSGS is directed at treating the cause when applicable, treatment of primary or idiopathic FSGS usually is nonspecific and targeted towards decreasing proteinuria, controlling BP, lipid control and low protein diet. In severe cases treatment is with steroids (tapering dose for at least 6 months) and for those who develop complications or are intolerant cytotoxic therapies like cyclosporine, tacrolimus, mycophenolate or cyclophosphamide. There are experimental therapies that include plasmapheresis.

 

It has long been speculated that there is a permeability factor playing a major role in the pathogenesis of idiopathic FSGS.

Recently it has been found out that suPAR (Soluble urokinase plasminogen activator receptor) is elevated in up to 2/3 of patients with primary FSGS. Evidence that higher SuPAR levels correlate with increased risk for recurrent FSGS after transplantation in patients with FSGS further supports the theory of this circulating factor in the pathogenesis of this condition. Importantly, molecular studies have also shown that the molecular size of suPAR is very close to the predicted molecular size of the “permeability factor” that has been considered to play a major role in the pathogenesis of idiopathic FSGS.

 

How does suPARwork?

 

suPar activates the podocyte beta 3 integrin (necessary for anchoring the podocyte foot processes to the glomerular basement membrane & also maintain cellular structure) causing foot process effacement, proteinuria & glomerulopathy.  Since it plays a major role, removing this factor by plasmapheresis or interfering SuPAR- beta 3 integrin interaction through antibodies will abrogate the pathogenesis of this disease

 

This opens up the therapy of plasmapheresis for such patients. It not only potentially keeps patients away from renal replacement therapy, but also may inhibit the progression of the disease at early stages to prevent its complications. However, It has to be noted that plasmapheresis has been shown to be effective in some patients with recurrent FSGS in a renal allograft, but not in patients with FSGS in their native kidneys. Could this be explained by presence of more than one such circulating factors or could it be due to patient selection?

 

For now, it is exciting to know more and more “idiopathic” glomerulopathies have prospects of entering the ‘treatable’ category of kidney diseases

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