Diabetes and CKD: Pitfalls - Monitoring response to therapy

There are two important issues to remember when assessing glucose control in patients ESRD, one relating to immediate blood sugar measurement, and another relating to longer term diabetes control.

The first has previously been mentioned on this blog. The use of icodextrin in PD solutions is increasingly common as a means of increasing fluid removal with less absorption of the solute. Icodextrin is not generally metabolized in the peritoneum but small quantities can cross into the systemic circulation where it is metabolized to maltose. Some commercial blood sugar test strips are unable to differentiate between glucose and maltose in the serum. This is not normally an issue because there is very little sugar apart from glucose in the blood. However, in patients on PD, the presence of maltose can lead to falsely elevated blood sugar readings with certain analyzers. This has lead to at least one death in a patient who was inappropriately treated with insulin in this setting. Of course, icodextrin is not the only potential source of maltose - certain IG preparations can also contain maltose resulting in similar presentations.

Traditionally, long-term monitoring of glucose control is done by regularly measuring HbA1c levels. However there are some concerns regarding the use of HbA1c in dialysis patients. RBCs in patients with ESRD tend to have shorter half-lives while the use of EPO appears to affect Hb glycation in unpredictable ways also. The relationship between HbA1c and mortality in dialysis patients is complex and contradictory results have been noted in various studies. A recently published study using data from the DOPPS study found that HbA1c was associated with mortality but only at substantially higher levels that would typically be considered normal.

One possibility is to use alternative measures of glycemic control such as glycated albumin or fructosamine. These have the advantage of not being affected by the Hb concentration. However, in contrast to HbA1c, they measure short-term glucose control only - for example, glycated albumin is a marker of glucose control over a period of about 17 days. One recent study found a significant association between glycated albumin and mortality while HbA1c was not as useful. It's possible that the reduced association between HbA1c and glucose control in diabetics with ESRD may be a contributing factor in recurrent episodes of hypoglycemia in some patients.

eJournal Club - Session length and weight gain

This month's eJournal club concerns a paper published by a fellow from our institution that attempts to get to the bottom of an interesting question: in patients with a high interdialytic weight gain (IDWG), is the dialysis session length (DSL) or the total volume gained more important? Both of these have been associated with increased mortality and both lead to an increased ultrafiltration rate (UFR). However, because they are interrelated, it is difficult to say which is more relevant.

For this study, the authors looked at more than 14,000 patients attending dialysis in the US. They excluded patients at extremes of session lengths and those who did not gain any weight between sessions. Patients with a URR less than 65% were also excluded to rule out any effects of underdialysis. The mean IDWG and DSL over 30 days were chosen as the exposures of interest. Interestingly there was high correlation between the 30-day IDWG and DSL and the 60 and 90-day means. The outcome was death from any cause. For the purposes of the analysis, the participants were divided into 2 groups for each exposure - less than or greater than 3kg IDWG and less than or greater than 240 minutes for DSL. A matched case-control study design was used.

Not surprisingly, the patients with higher IDWG tended to be younger, male, AA, had higher blood pressure and a higher prevalence of diabetes and CHF. Patients with lower DSL were more likely to be female, older and were less likely to have diabetes, CHF and CAD.

For the DSL analysis, lower DSL was associated with a HR of 1.32 (1.03-1.69) for mortality after full adjustment. For the IDWG analysis, increased IDWG was associated with a HR of 1.29 (1.01-1.69) for mortality. Thus both DSL and IDWG were independently associated with mortality.

What does this study mean for clinicians. It suggests that targeting both of these interventions could be useful. However it should be pointed out that this is an observational study and that they could not show that changing any of these exposures changed risk. Also, the because of the study design, the authors can only state conclusively that both are associated with mortality and not which one is more important. These conclusions may seem obvious but it is important to have good evidence to present to patients who may be frustrated with our requests to increase times and reduce fluid intake.

Head over the eJournal Club to continue the discussion of this paper.

Hypothermia Protocol and Dialysis

I recently received an inpatient consultation to see a CKD 5D patient. The reason for consult, as is mostly the case with dialysis patients was that he “needs hemodialysis”.

This dialysis patient wasn’t the average bear though. He had had a witnessed cardiac arrest, was treated by EMS, and defibrillated. He had a return of spontaneous circulation after being pulseless for 20 minutes. As soon as he got to the ER, he was initiated on our standard institutional therapeutic hypothermia protocol.  I was called in to dialyze him because (it wasn’t his usual day) the cardiologist wanted to perform a left heart cath on him the following day, and they “did not want dialysis to interfere with that schedule”. My clinical assessment did not reveal a severe degree of volume overload. He wasn’t hyperkalemic, and had only a mild degree of lactic acidosis that was nicely compensated by him being appropriately ventilated. Due to the concerns that I talk about below, I did not see an emergent reason to dialyze him.

I would like to focus on a few teaching points from a nephrologist’s perspective that I took away from this scenario:

1. Therapeutic hypothermia entails cooling post cardiac arrest patients to 32-34 degrees Celsius, ideally within 6 hours of a cardiac arrest.  Both intravascular and surface cooling methods are used. At my institution, the protocol involves administering up to 3 liters of 0.9% saline (which has been cooled to a temperature of 4 degrees Celsius), over an hour. This is complemented by cooling vests. Once target temperature is reached, the cooling phase is continued for 12-24 hours, after which the patient is rewarmed gradually at the rate of 0.5 degrees Celsius/hour.
2. Sub-physiological body temperatures expectedly have adverse effects. Hypothermia can hamper leukocyte function, increasing infection risk later. Cardiac effects include bradycardia and prolonged QT interval (both were present in this patient). Finally, for us nephrologists, here are some adverse effects and pertinent points that we need to keep in mind for such patients:
3. Hypothermia can cause hypokalemia via two different mechanisms. Low temperature causes a transcellular shift of potassium in to the intracellular compartment. This effect is possibly mediated by increased beta adrenergic and sympathetic activity. In fact, hypokalemia in the setting of hypothermia must be repleted extremely cautiously, if at all, given the risk of rebound hyperkalemia as potassium moves back out of the cells when the patient is rewarmed. This rebound hyperkalemia can be frequently fatal due to arrhythmias.
4. The second mechanism by which hypothermia causes hypokalemia is by the induction of polyuria, also known as “cold diuresis”. This hypokalemia is mediated by increased urinary flow, and is seen in conjunction with hypovolemia, hypophosphatemia, and hypomagnesemia. I didn’t observe any of these in my patient, maybe because of his oligo-anuric status at baseline. Nevertheless, close monitoring of volume status and electrolytes is required.
5. Hypothermia interferes with platelet function and with the clotting cascade. In fact, as per this review, 22% of patients had bleeding post-hypothermia induction. That might be a concern when making the decision to dialyze post-hypothermia patients with heparin.
6. The other issue that I ran in to, that was specific to dialysis patients, was the concern about the patient’s temperature. As we know, most HD machines warm blood before returning in to the patient. With most machines, the warmer cannot actually be turned off and only goes as low as 35 degrees Celsius. In other words, dialysis can inadvertently warm the patient up to this temperature (from the target temp of 32 degrees, per the hypothermia protocol)! CRRT machines do have adjustable temp settings that goes down to 32 degrees, so that might be a safer alternative. Given the risk of inadvertently warming the patient, and because I did not see any emergent indication for dialysis, I did not dialyze the patient. I believed that in that situation, his hypothermia protocol took precedence over dialysis.

In my experience, I have observed that referring non-renal physicians often consider inpatient hemodialysis an ancillary service, akin to placing an order for an x-ray or a lab draw. Seasoned fellows have heard this phrase all too often, “I want you to come down and dialyze this patient”. You are then left with the unenviable task of explaining to the non-renal physician that the decision to dialyze would be made by the nephrologist after proper assessment of the patient (isn’t why they consulted you in the first place?). Let’s not allow our familiarity and comfort with dialysis technology lull us in to putting our guard down. Dialysis is an inherently intense and complicated procedure where multiple clinical parameters need to be closely watched. It’s a fact that is often lost in translation.

Posted by Veeraish Chauhan

Extended High Cut-Off (HCO) Hemodialysis for Myeloma Cast Nephropathy

There has been much recent interest in novel extra-corporeal treatments for removal of nephrotoxic free light chains (FLC) in myeloma cast nephropathy. HCO dialyzers employ high flux membranes with particularly large pores (up to 50kDa Vs 15kDa for conventional high flux) facilitating the removal of large plasma proteins such as FLC (kappa and lambda light chains have molecular weights of 22kD and 45kD respectively). HCO-HD may also be potentially beneficial in rhabdomyolysis with myoglobin having a molecular weight of 17kDa.

Extra-corporeal removal has primarily been achieved using plasma exchange and has long been a controversial topic in nephrology. HCO dialyzers are much more efficient at clearing FLC compared to plasma exchange. Multiple case reports have suggested a benefit to early use of HCO-HD in cases of cast nephropathy and a study by Hutchinson CA et al demonstrated an early reduction in FLC to be associated with renal recovery. Another paper from the same group reported on 67 patients with AKI due to cast nephropathy who received HCO-HD with modern chemotherapy. The majority of patients had sustained reductions in serum FLC concentrations (76%) and a high rate of independence of dialysis (63%). The HD regime used Gambro HCO 1100 dialyzers and was aggressive, with almost daily 8-hour sessions for the 12 days. After this, the schedule drops back to alternate days and finally to three 6-hour sessions per week after day 21. My limited experience with this regime in 2 patients demonstrated a need for regular phosphate and albumin repletion and careful monitoring of other electrolytes.

Obviously HCO-HD will only remove FLC and will not stop their production. Therefore, for a sustained response, patients need to be a on a chemo-sensitive regime. The above studies have demonstrated that patients who need a break in chemotherapy do worse, as do those with signs of chronicity on renal biopsy.

The following criteria are suggested before considering HCO-HD in patients with AKI due to cast nephropathy:

1.       Chemo-sensitive regime; bortezomib is frequently employed

2.       High serum FLC levels (>500mg/l; usually much higher)

3.      Low levels of interstitial fibrosis & tubular dropout on biopsy (i.e. evidence of salvageable kidneys)

A randomized controlled trial, led by Dr. Hutchinson, in the UK is currently on-going (Eulite Trial) which will compare conventional high flux HD with HCO-HD in patients receiving chemotherapy (bortezomib or thalidomide plus dexamethasone). HCO-HD certainly appears to be more efficient than plasma exchange at reducing FLC levels but at this point, its precise role in the management of cast nephropathy is unclear. We await the Eulite trial to hopefully clarify the potential benefit of HCO dialysis in this situation.

Hemodialysis vs. Peritoneal Dialysis

My attention was caught by the recent article in CJASN which compared the mortality of peritoneal dialysis (PD) and hemodialysis (HD) patients in the first 2 years of dialysis therapy. When comparing survival outcomes of PD and HD patients, the data we have so far is based on observational studies. A randomized controlled study has never been successfully completed because of difficulties in randomization. The only randomized study so far - the NECOSAD study (Netherlands) managed to randomize only 5% of the eligible subjects3.  

Most of the observational studies looking at survival had methodological limitations like suboptimal adjustment for modality switch over time (PD patients more likely to switch to HD), inability to account for time-varying confounding by laboratory values and inappropriate adjustment for the differential longitudinal censorship of transplantation across modalities (PD patients more likely to get a transplant). While analyzing such time-varying covariates which are simultaneously confounders as well as predictors of outcome and subsequent exposure, traditional methods like logistic or proportional hazards regression are biased and hence they pose unique analytical challenges. Hence a new statistical model – a Marginal Structural Model (MSM) which employs  inverse probability weights (IPWs) to determine the effects of these time varying covariates on the primary outcome (which was survival  in this study) was utilized  in this study. In order to adjust for the effect of each dialysis modality and censorship from transplantation, a combination of inverse probability of treatment weights (IPTWs) and inverse probability of censoring weights (IPCWs) was used. The IPTW (or IPCW) will have estimated probabilities of treatment (or censorship) using baseline covariates as the numerator and estimated probabilities of treatment (or censorship) using baseline and time-dependent covariates as the denominator. The MSM helped to derive meaningful survival data, adjusting for the above mentioned confounders

The study used information from two large databases viz. USRDS and Da Vita, providing a large cohort of almost 24000 incident dialysis patients. Separate analysis was conducted using a Kaplan–Meier survival curve, cox proportional hazards and the MSM model. A 48% greater survival for incident PD patients at 2 years was found using the MSM model. These findings were in contrast to findings in other studies in the past which showed either no difference in survival or marginal survival advantage especially in the first year for PD compared to HD5. Additionally, a comparison between the cox model and the MSM   demonstrated that the time-dependent confounders determined the difference in survival. Changes in modality during the first 2 years of dialysis affected the survival patterns over time and the reason for this trend is not completely understood at this point. This study supports greater use of PD in the treatment of ESRD patients especially in US where less than 8% of prevalent patients with ESRD are on PD.A comprehensive dialysis modality education program should be encouraged to expand the practice of PD.

See these two previous posts on the debate between PD and HD.

Posted by Bijin Thajudeen

Self-cannulation

Bill Peckham, the author of the excellent patient advocacy and home dialysis blog: dialysis from the sharp end of the needle has been on dialysis since 1990 and home dialysis since 2001 where self-cannulates using the buttonhole method. Last year he posted a video on Youtube that I only came across today. It shows his technique of needle insertion. I have often wondered how patients manage to cannulate themselves at home and this demonstrates it very nicely. I am full of admiration for my patients.

 

Hemoglobin Targets in CKD

For anyone who would like to read a thorough review of the current evidence with regard to Hb targets and the use of ESAs in  patients with CKD and those on dialysis, I strongly recommend the review published in Nature Reviews Nephrology this month. The field of anemia treatment if CKD has changed completely in the last 10 years. Hb targets have gotten considerably lower and the "one size fits all" model is changing into a model based on individualized Hb targets.

Two questions remain to be answered fully:
- In patients with CKD, is it the high Hb that is dangerous or is it the high doses of ESAs?
- What do we do with patients on dialysis who are not even achieving the new lower targets despite escalating doses of an ESA

My personal bias is that it is the ESA that is the problem rather than the Hb dose. Observational studies have shown that patients who achieve high Hb targets without the use of an ESA have no increased risk of CVD. ESAs are known to activate the vasculature and potentially increase the production of profibrotic and prothrombotic circulating factors. Patients who require very high doses of an ESA to achieve a particular Hb target are a high risk group and it may be that the requirement for such high doses is a marker of disease burden.

The Normal Hematocrit Study (NHCT) was published in the NEJM in 1998 and reported that there was a non-significant increase in mortality in patients in the high Hb group. However, there was a benefit in terms of QOL in patients with a higher Hb. This study has been criticized before and further analysis of the outcomes has shown that when the patients were followed for a longer period, there was a statistically significant increase in mortality in the high Hb group. Last year, a paper in KI reanalyzed the results of this study and found that this increase in mortality was evident even earlier that had been reported.

There was another fascinating finding in this report. The original study reported quality of life in patients based on achieved Hb levels. Thus, higher Hb was associated with better QOL irregardless of whether or not the patient was in the high Hb group. There was no difference in QOL between the randomized groups. In other words, it wasn't the ESA that was making the difference - there was a difference between those patients who had high Hb levels compared to those who did not reach those levels that was not related to the use of an ESA: patients who are healthier and respond better to an ESA have higher QOL scores! There was a misinterpretation of these results to mean that high ESA doses were associated with better QOL which has subsequently been proved wrong.

There was an accompanying editorial with that KI article that is definitely worth a read and advocates for new standards in the reporting of clinical trials.

Is it time to wake up to online Hemodiafiltration?

There has been a lot of interest recently in online Hemodiafiltration (olHDF) with multiple studies  published in the past year. It is a technique which has gained favor in Europe (albeit with a lack of hard evidence) while being not utilized at all in the US for various reasons. HDF involves the addition of convective clearance, hemofiltration, to the diffusive treatment of hemodialysis (HD) which gives better clearance of middle sized uremic toxins. Very large volumes of plasma water are ultrafiltered using a high flux dialyzer with replacement solution needed to maintain fluid balance. As a large volume of fluid is infused directly into the patient, this infusate needs to be ultrapure with low levels of pyrogen and microbial contamination. The development of online generation of ultrapure replacement fluid, directly from the water treatment plant, has facilitated the roll out of olHDF in Europe. Safety concerns have also been addressed. Previously reported benefits, apart from middle molecule clearance, have included better phosphorous removal, improved intra-dialytic blood pressures, lower levels of EPO resistance, improved quality of life among others but hard outcome data has been lacking until recently. The past year has seen the publication of 3 randomized controlled trials examining olHDF versus conventional HD.

CONTRAST Study

The Convective Transport Study randomly assigned 714 patients to either olHDF or low flux HD. There was no difference between the groups in the primary outcome of all-cause mortality after a 3 year follow-up. However, in post-hoc analyses, receiving high dose olHDF (>22L of convective volume per session) was associated with a lower all-cause mortality compared to low flux HD (HR 0.62).

Turkish olHDF Study

This study randomized 782 patients to olHDF or high flux HD. The composite endpoint of all-cause mortality and nonfatal cardiovascular event rate was not different between the groups after a 2 year follow-up. However, again in a post-hoc analysis, a higher delivered dose of convective clearance (>17.4L, the median clearance) was associated with a lower risk of overall (RR 0.54) and cardiovascular mortality (RR 0.29).

Spanish olHDF Study

The latest study set out to deliver a high dose of replacement fluid and they succeeded (median convective volumes approximately 23L). They assigned 906 patients to either continue their current modality (mostly high flux HD) or switch to olHDF. The primary outcome of all-cause mortality occurred 30% less frequently in the olHDF group (p=0.01) after approximately 2 years.

Verdict: My previous experience with olHDF involved using it in an ad-hoc basis for patients with uremic symptoms despite ‘adequate’ KT/V urea or in patients with long dialysis vintage (extrapolating results from the HEMO study as high flux HD is a form of low dose HDF). Many European Nephrologists have presumed outcomes would be better but with very little data to back that up. We now have 3 RCTs suggesting a relationship between high dose olHDF and improved mortality. In our dialysis patients with such high mortality and with few interventions proven to impact this over decades, these results should be appreciated by the Nephrology community. It is at least time to reconsider the barriers to its use.

Posted by Paul Phelan

Skin Lesions in Dialysis - Part 5

Nail changes in renal failure:

Half and half nails (Lindsay's nails) can be found in patients with any degree of azotemia. The prevalence is about 21% in dialysis patients. the proximal half of the nail is white and the distal half is brown or pink. This color does not fade with nail pressure. The pathophysiology of the changes is not well understood but is thought to be due to increased beta-melanocyte stimulating hormone in the nail bed. This does not improve with dialysis.

Other changes are also seen in the nails of dialysis patients. Beau's lines are characterized by transverse deep depressions. Mee's lines have a single white band in the nail plate. Terry's nails present with the proximal 2/3 being wide and pale with the distal 1/3 narrow and red.

(Image on the left shows Beau's Lines [source], Image on the right show half and half nails [source])

This is the final post in the series on skin lesions in dialysis patients.

Posted by Andrew Malone

Skin Lesions in Dialysis - Part 4

Acquired Perforating Dermatoses:

Perforating dermatoses are a group of conditions characterized by transepidermal elimination of dermal material (collagen, elastic tissue or necrotic connective tissue) (CMAJ). APD is one of the 4 major perforating disorders:

• Reactive perforating collagenosis(inherited disorder of collagen perforation) 
• Elastosis perforans serpiginosa (elastic tissue perforation associated with Down syndrome and Ehler–Danlos syndrome) 
• Perforating folliculitis (perforation of necrotic material secondary to local trauma)
• Acquired perforating dermatosis. 

Historically there was a lot of overlap in terminology between these disorders. Acquired perforating dermatosis classically presents with severely pruritic follicular hyperkeratotic papules, sometimes umbilicated, on the hair-bearing limbs of adults. Generalized papules may also be seen. Acquired perforating dermatosis is a chronic disease, usually associated with diabetes mellitus or renal failure or both. In patients receiving dialysis, acquired perforating dermatosis occurs in about 10% of patients. It is also rarely associated with liver disease, malignant disease, hypothyroidism and HIV. Skin biopsy is required to diagnose APD. This reveals epidermal invagination or dilated hair follicle with a keratotic plug of keratin, collagen or elastic fibres and neutrophils. The pathophysiology is not well understood. Topical and systemic retinoids, topical corticosteroids and keratolytics, UVB, psoralen and UVA, allopurinol, cryosurgery and photodynamic therapy have all been considered in the treatment of this disorder.

Image shows: Follicular keratotic papules consistent with acquired perforating dermatosis distributed diffusely over the legs (A) and buttocks (B). Skin biopsy (C) showing a hair follicle with perforation extending into the dermal tissue, which contains a tract of necrotic tissue debris with degenerate elastin fibres. (From CMAJ)

Posted by Andrew Malone 

Skin Lesions in Dialysis - Part 3

Nephrogenic Systemic Fibrosis (NSF)

No post or summary on skin disorders in renal failure can omit NSF. This has been mentioned in multiple previous posts on RFN - although never summarized:

The first cases of this disorder were noted between 1997 and 2000. Nearly all have been in patients with gadolinium exposure. Most of these patients had severe CKD or were on dialysis. The onset of NSF post gadolinium exposure ranges from 2 months to 15 years. The risk of NSF in dialysis patients has been reported as between 2.5 and 5%. Most centers have stopped using gadolinium if the GFR is less than 30ml/min/1.73m2. Starting or increasing EPO dose has also been associated with NSF. This disorder is a systemic disease. Skin disease typically presents with symmetrical, bilateral fibrotic, indurated papules, plaques or subcutaneous nodules. Lesions start in the hands, feet and ankles and move proximally. Rarely are lesions found on the abdomen and the head is spared. Lesions are edematous and may look like cellulitits initially. Sharp pain, pruritis and burning are also a feature. Joints lose flexibility due to fibrosis. Histological findings are variable: Increased dermal cellularity, CD34+ cells with tram tracking, collagen bundles, septal involvement and osseous metaplasia are typical findings. A comprehensive screen for other causes of severe skin disease is important. NSF has a poor prognosis and one review of the literature suggests a mortality of 28%. There is no treatment for NSF other than recovery of renal function. The preventative measure of avoiding gadolinium exposure in those at risk has significantly reduced the incidence of NSF. A good website by The International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) can be found at http://www.icnfdr.org/.

Posted by Andrew Malone

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.

For example:

Discoid Lupus Erythematosus (DLE); these lesions are thick and scaly, plug the hair follicles, appear usually on surfaces of the skin exposed to sun (but can occur in non-exposed areas), tend to scar, and usually do not itch.

Acute Cutaneous Lupus Erythematosus (ACLE); Confluent erythema and edema, erythematous macules and papules that eventually become confluent and occur in areas exposed to the sun and can be triggered by sun exposure.

Subacute Cutaneous Lupus Erythematosus (SCLE); is a nonscarring, non–atrophy-producing, photosensitive dermatosis. SCLE may also occur in Sjögren syndrome, associated with deficiency of the second component of complement (C2d) or it may be drug induced.

50% of all people with lupus experience sensitivity to sunlight and other sources of UV radiation. 

The following to disorders are very similar but have very different outcomes:

Porphyria Cutanea Tarda (PCT)

This is the most common porphyria. It is caused by the accumulation of uroporphyrinogens, which cause a phototoxic skin reaction and liver abnormalities. PCT is due to low uroporphyrinogen decarboxylase activity. Spontaneous PCT can be caused by alcohol, hepatitis C or HIV infection, hemochromatosis or estrogen excess. Iron overload is a well-recognized trigger for PCT and thus something to be wary of in dialysis patients. The pathogenesis of this disorder in dialysis patients may also be due to the fact that they cannot excrete porphyrin precursors in the urine. The incidence of PCT in hemodialysis patients is between 1.2 – 18%. Clinically patients have fragile skin, blisters, vesicles and bullae in sun exposed in especially the dorsum of the hands. Sclerodermoid changes can occur in any skin area. Other clinical manifestations include hypertrichosis, hyperpigmentation, dark urine and pruritis. Histologically PCT is characterized by subepidermal separation of the skin with little or no inflammation. On IF, IgG and C3 can be seen along the dermoepidermal junction. Diagnosis in dialysis patients is by looking at the fractional levels of plasma porphyrin precursors. Treatment includes avoiding sun exposure and regular phlebotomy. Higher doses of ESA are usually required to avoid anemia. Chloroquine has also been used for this disorder but with varying results.

Pseudoporphyria (PP)

This disorder is also known as bullous dermatosis of ESRD. It has exactly the same clinical and histopathological changes as PCT (except there are no sclerodermoid changes or hypertrichosis in PP). However, there are no biochemical abnormalities of heme metabolism or porphyrins. This distinguishes it from PCT. One must be aware, however, that plasma uroporphyrin is increased at baseline in dialysis patients. Its incidence in dialysis patients is the same as for PCT. PP is associated with UV exposure, diuretics, NSAIDS (naproxen), antibiotics, antifungals (voriconazole), retinoids, finasteride, imatinib and others. In ESRD patients free-radical injury due to reduced glutathione levels in plasma and red blood cells is thought to play a role in PP. Treatment includes removal of any offending drugs and N-acetylcysteine. Symptoms may take months to improve.

Posted by Andrew Malone

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 weak on.  Patients on dialysis are a unique group in whom we see diseases that are either vanishingly rare or not seen in non-renal patients. This includes diseases of the skin. I will give an overview of some of these conditions. Markova et al, gives a good overview of most skin disorders peculiar to renal patients. This will be part of a series of posts on skin disorders in renal patients.

1)Skin disorders involving calcification in renal failure.

Calcium and phosphate deposition in the skin has been said to be a contributing factor to pruritus that is common in renal failure as well as in other skin disorders. Here are two contrasting calcium related skin disorders with very different outcomes.

Calciphylaxis. In this disorder calcification of the small vessels of the dermis and subcutaneous tissues occurs. This leads to vessel thrombosis, tissue infarction and skin necrosis. It occurs in 1-4% of dialysis patients. Risk factors include hyperparathyroidism, an elevated calcium-phosphate product (>70 mg²/dl²), diabetes mellitus, female sex, obesity, warfarin use, and protein C or S deficiency. 1-year survival after the diagnosis of calciphylaxis is about 50%. In calciphylaxis patients get very painful violaceous reticulated plaques that are well defined and deep. These lesions develop into deep non-healing ulcers that can become gangrenous. Sepsis is the most common cause of mortality. Treatment options include a low phosphorous diet, normalizing calcium and phosphate with non-calcium based phosphate binders and low-calcium dialysate. Sodium thiosulphate 25g VI over 30 minutes three treatments per weeks has been shown to improve lesions and should be continued for 2 months beyond the resolution of lesions.

Calcinosis cutis. This refers to calcium deposition in the skin and is a subtype of calcinosis, a condition describing calcification in vessels and organs. Patients with calcinosis cutis get painless flexural infiltrating plaques at periarticular sites. The size and number of plaques corrolate with degree of hyperphosphatemia. Unlike calciphylaxis this disorder does not cause skin necrosis.  Risk factors include low albumin, high phosphate, high alkaline phosphatase and morbid obesity. It occurs in about 1% of dialysis patients. There is no gold standard treatment but normalisation of calcium and phosphate can cause lesions to regress.

Posted by Andrew Malone