Page Kidney

Patient with a history of kidney transplant s/p biopsy 2 weeks prior now undergoing chemotherapy treatment for leukemia develops acute abdominal pain, worsening renal function and hypertension. Renal US followed by CT are shown below:

Renal US with dopplers

Renal US longitudinal view

Abdominal CT with renal tx on right lower quadrant

 

Abdominal CT with red-marked kidney parenchyma

Diagnosis: Page kidney is a condition where extrinsic renal compression from a haematoma or mass results in hypertension and loss of renal function. This condition was initially described by Irwin Page in an animal model with cellophane papers wrapped around the kidney in 1939 and, subsequently, clinically in 1955.Most cases are caused by a subcapsular haematoma following blunt trauma or invasive procedures (eg. renal biopsy). Few cases of spontaneous hematoma have also been reported. Acute renal failure is due to a decreased perfusion of the compressed kidney as a result of pressure exerted by the subcapsular haematoma. In our case, the drop in platelets (4,000) after chemotherapy might have precipitated the bleeding from the previously biopsied site.

Treatment involves relief of the pressure and restoration of blood flow by percutaneous drainage. Nephrectomy is recommended in cases not resolved by interventional nephrology. Conservative course (observation and medical management) has been performed in some case reports.

eJournal Club - Kidney Biopsies

This month's eJournal Club concerns a paper (with an accompanying editorial) reporting the experience of renal biopsies in Norway. One issue that arises again and again is whether or not patients should undergo outpatient biopsies. The argument against this is that many complications occur more than 8 hours following a biopsy and that the complication risk is too high to allow patients to remain unmonitored at home. These recommendations were based on older data which dated from before the era of live ultrasound and the more modern biopsy needles. More recent studies have suggested that outpatient biopsies are safe and I had a conversation with one attending at the ASN last year who was surprised that everyone was not doing outpatient biopsies because they had been doing it without a problem for years.

This paper, while not specifically addressing the issue of outpatient vs. inpatient biopsies, should alleviate some of the concerns that people have. After 9288 biopsies, the rate of serious complications was 0.9% (transfusion or surgical intervention). This is similar to recently published studies. There were no deaths during the 20 years covered by the study. There was an increased risk of bleeding in patients with a low GFR, uncontrolled hypertension, older age and acute kidney injury. Notably there was no difference in bleeding complications when 14G needles were used as opposed to 18G needles although less glomeruli were obtained with the smaller needles. 

There an interesting point for discussion here - in the course of the study, there was a marked decline in the number of nephrologists performing biopsies. The majority of biopsies are now performed by radiologists. These radiologists are more likely to use smaller needles and thus get less tissue. Should nephrologists take back the renal biopsy? Should we be more assertive in insisting that larger needles are used to ensure adequate biopsies? Head over the eJC for the discussion.

To biopsy or not to biopsy

Diabetes is a common cause of CKD and the prevalence of diabetic nephropathy is increasing. A question that sometimes arises in the clinic is when it is appropriate to biopsy a patient with a presumptive diagnosis of diabetic nephropathy and are there any signs that may suggest that there is an alternative diagnosis. It is reassuring that recent data have suggested that renal biopsies in low-risk patients are associated with a very low risk of adverse consequences but I still don't think that anyone would recommend biopsying all patients who present with diabetes and CKD.

So how do you decide who to biopsy. It has been suggested in the past that the presence of hematuria was associated with a lower incidence of true diabetic nephropathy while diabetic retinopathy suggested the opposite. A study was recently published in the Journal of Diabetes Investigation which looked at the results of renal biopsies in patients with diabetes. In total, 55 patients with T2DM were included in the study. These were not random patients with diabetes; all of them had a clinical course which suggested that an alternative diagnosis might be present. 30 of the patients had true DN while 25 had no evidence of diabetes. Of these 13 had IgA nephropathy. One patient had a crescentic GN. The duration of diabetes was not a good predictor of the likelihood of DN. This is not altogether surprising when you consider that this is duration since diagnosis and the patients may have had diabetes for signficantly longer without being aware. Poor glycemic control and the presence of diabetic retinopathy were significantly associated with a higher likelihood of DN. No patient in the non-DN group had diabetic retinopathy which again goes to show the usefulness of this examination in stratifying patients with presumptive diabetic renal disease. This goes to show that the advice that we have been getting in the past is good - the absence of diabetic retinopathy should make you suspect an alternative diagnosis.

One interpretation of this study is that patients with atypical presentations and diabetes should have a biopsy because there is a good chance of an alternative diagnosis. Another, more conservative interpretation is that even in patients where there is a high pre-test probability of a non-diabetic lesion, the majority of patients will have diabetic nephropathy and in those that don't the treatment will most likely be the same in any case.

Still mysterious: the elusive circulating factor for FSGS

Important new findings were recently published in relation to proteinuria and FSGS, which are definitely of interest to our community.

First, the punch line:

There is new evidence for a “circulating factor” in recurrent FSGS in a fascinating case of a re-transplanted kidney (here)

BUT

There is growing evidence that suPAR is a non-specific marker of kidney disease and therefore not likely to be the “circulating factor.”(here)

In fact, it appears that it is non-specifically found in CKD, and correlates with a declining GFR.

Now for some details:

The re-transplanted kidney

A letter to the NEJM editor (here) describes an amazing case of resolution of recurrent FSGS after re-transplantation. 

A 27 year old patient with primary FSGS receiving a kidney from his healthy 24 year old sister developed proteinuria in the nephrotic range (up to 25 g/day!) within 2 days of transplantation, and had no improvement after plasmapheresis and standard immunosuppressive treatment. A renal biopsy confirmed foot process effacement, the first hallmark of recurrent podocyte damage heralding recurrent FSGS. Incredibly, with all appropriate consents and institutional approval, the transplant team removed the allograft from Patient 1 and re-transplanted it into another patient who had ESRD due to diabetes. Within 3-4 days, the proteinuria resolved and a repeat biopsy showed resolution of foot process effacement and re-establishment of a normal podocyte architecture. Eight months later, Patient 2 is reported to be doing very well, with good allograft function and no proteinuria.

This case demonstrates in a remarkable way that recurrent FSGS results from an elusive “factor” rapidly produced by the recipient (with primary FSGS), and that the allograft itself can remain fully functional if removed from the influence of this “factor” and placed in another patient.

suPAR is not suPER specific

What may have seemed to be exciting news in 2011, namely the notion that soluble uPAR may be predictive of recurrent FSGS (here), appears to be unfortunately evolving into yet another unsuccessful attempt to identify the ever elusive circulating factor.

Recent work published in Kidney International by Maas et al. (here) confirms that suPAR is not able to distinguish between idiopathic FSGS, secondary FSGS or minimal change disease. 

This is actually not surprising, because a closer look at the clinical data in Wei et al. (here) reveals that the admittedly arbitrary cut-off for separating primary FSGS from all other glomerular disease (3000 pg/ml) did not hold up when tested among their patient cohorts with idiopathic, recurrent versus non-recurrent FSGS (all had suPAR> 3000 pg/ml, thus suPAR could not predict the recurrent from the non-recurrent cases). 

The second figure in the Maas et al. paper may help explain this conundrum: they show a negative correlation between suPAR and eGFR, meaning that as GFR drops, suPAR levels rise, which essentially means that suPAR is simply a marker of CKD.

Future work will no doubt continue to address these issues, but the apparent lack of specificity of suPAR for FSGS casts serious doubt on its proposed role as the circulating factor.

So, the search is still on!!!

Handling anticoagulation peri-kidney biopsy

Kidney biopsy is considered the most invasive procedure nephrologists are involved. Though complication rates are small, bleeding requiring surgery has been reported to occur in 1 in 1,000 kidney biopsies. More commonly, patients may develop a decrease in hemoglobin by 1 point (~50% of cases) and/or gross hematuria (3-18%). The risk of bleeding complications become much higher in patients that require peri-biopsy anticoagulation.

A new evidence-based guideline was just published on Chest 2012, summarizing the best approach to anticoagulation in a number of different scenarios. Overall, the new recommendations are more conservative than before regarding anticoagulation peri-procedure.

To illustrate that, let’s use a theoretical patient on anticoagulation with coumadin (6mg daily) due to Factor of V Leiden mutation and prior history of thrombosis (more than 6mo ago).

In preparation for the procedure, the physician would recommend stopping coumadin 5 days prior to the kidney biopsy and bridging with either UFH or LMWH. This is usually started on day 3 prior to the procedure. The major difference in approach now is related to when should the bridging anticoagulation be stopped and restarted. The novel guidelines recommend the following:

* If on IV heparin, stop infusion 4-6 hours prior to procedure

* If on LMW, last dose should be 24 hours prior to procedure (rather than 12 hours before)

* Resuming coumadin should occur 12-24 hours after procedure if no evidence of bleeding

* Bridging anticoagulation with LMWH or UFH should be restarted 48-72 hours after the procedure (rather than 24 hours after surgery). Since most of the bleeding after kidney biopsy will occur in the first 24 hours, I believe delaying for another 24 hours would only be warrant in major surgeries with higher bleeding risks)

Most of these recommendations are grade 2C (weak), therefore individual interpretation is warranted.

My take-home summary of anticoagulation peri-kidney biopsy in high risk patients for thromboembolism would be:

Stop coumadin 5 days before procedure; admit the patient with renal failure 3 days prior to biopsy for bridging with UFH; stop UFH at least 4 hours prior to procedure; resume coumadin/UFH 6-24 hours after bx if no evidence of bleeding (stable Hb, vital signs and no significant hematuria).

Though this is a general suggested approach, remember to assess the thromboembolic risk for each individual patient before proceeding with a kidney biopsy. As an example, I would favor restarting anticoagulation much earlier after bx in a patient with history of multiple clots (6 hours after biopsy).

Below additional general recommendations about anticoagulants from the new guidelines:

- Dosing of UFH: 80U/kg bolus followed by 18U/kg/hour

- Dosing of coumadin: loading with 10mg daily for first 2 days [[personal opinion: this loading dose may be too high for elderly or cachetic patients]]

- Dosing of enoxaparin: 1mg/kg BID; if GFRb below 30 ml/min: 1mg/kg daily

- Dosing of fondaperinox: 5mg daily if less than 50kg; 7.5mg if 50-100kg and 10mg if more than 100kg. Avoid if GFR less than 30 ml/min.

- Dosing of dalterapin : 200 U/kg daily. Accumulation expected in renal failure but no specific dose adjustment has been recommended, so should likely be avoided until trials available.

- Despite recent publications about benefits of genotyping in predicting response to coumadin, the guidelines recommend against this practice.