Biweekly Internal exam September

 

1) Anatomical Diagnosis :

Given the history of Dyspnea with pedal edema, facial puffiness, abdominal distension along with reduced urine output the location that would first strike my mind are the kidneys.

For patients presenting to us with Pedal edema, dyspnea, these are few differentials we look into:

* Renal Failure

* Congestive heart failure

* Chronic liver disease

* Hypoaluminaemia

* Anemia

but here the the patient also seems to be having reduced urine output so the anatomical location would be due to glomerular injury

Also the patient complains of chest pain along with palpitations - would look for any cardiac etiology

After reviewing the investigation:

Her Serum creatinine has been on the higher side since 6 months - 4.4 mg/dl. Her serum creatinine and blood urea have raised over the last 6 months.

6 months back,    Serum Creatinine was 4.4 mg/dl and now it rose to 6.4 mg/dl

Blood urea rose from 72mg/dl to 92mg/dl

Her Current eGFR is 6ml/min/1.73m2

Her reports also show - Hypokalemia, anemia - microcytic hypochromic type, Metabolic acidosis, significant albuminuria >2.5g/day along with presence of red cells in the urine

Her kidneys appear to be normal in size. Her TLC is within the normal range

Her ecg shows no significant changes that would explain her cardiac etiology owing to her chest pain.

ANATOMICAL DIAGNOSIS :

Glomerular injury - Nephritic - Nephrotic syndrome

Could be IgA nephropathy

ETIOLOGICAL DIAGNOSIS:

Secondary to long standing history of diabetes along with hypertension.

Also because of toxins affecting the glomeruli such as tobacco, since 8 years

2) Azotemia :

Azotemia is the accumulation of renal nitrogenous was products in the blood without being excreted.

(BUN & creatinine)

Looking at her eGFR as low as 6 ml/min/1.73m2 the reason for azotemia can be well explained.

Anemia:

Her peripheral smear shows a microcytic hypochromic picture

Could be due to Anemia of chronic disease

https://jasn.asnjournals.org/content/23/10/1631

Here are some mechanisms that lead to Anemia in CKD:

Uremic inhibition of erythropoiesis

Reduced erythrocyte survival

Also because of reduced renal clearance, there's an increased in the hepcidin levels which leads to reduced erythropoietin production. Hepcidin also reduces iron absortion by acting on the duodenum and mobilization of iron from body stores

Hypoalbuminaemia

Albumin is being lost in the urine due to glomerular capillary wall injury and also maybe be due to reduced tubular reabsorption of albumin.

https://nephcure.org/livingwithkidneydisease/understanding-glomerular-disease/

Metabolic Acidosis

In patients with Renal failure like in our case, impaired excretion of nitrogenous waste products leads to increase in acid load which inturn leads to metabolic acidosis.

Over time, severe metabolic acidosis with a large anion gap tends to develop due to reduced tissue perfusion or sepsis.

Metabolic acidosis in CKD stimulates production of  angiotensin II, aldosterone, and endothelin-1 that lead to ncreased kidney acid excretion overtime they promotes inflammation and fibrosis

 Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. 

https://jasn.asnjournals.org/content/31/3/469

In patients with renal failure the increased acid retention leads further damage of the kidneys.

3) Rationale and  efficacy for some of the drugs administered such as oral and iv bicarbonate?

1. This was a prospective randomized controlled trial performed at London, UK, Published in 2008

               https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736774/

P - 134 adult patients with CKD (creatinine clearance [CrCl] 15 to 30 ml/min per 1.73 m2) were randomly selected and serum bicarbonate 16 to 20 mmol/L to either supplementation with oral sodium bicarbonate or standard care for 2 yr. 

I - 67 patients received oral bicarbonate therapt whereas the other 67 were put on standard therapy

Compared with the control group, decline in CrCl was slower with bicarbonate supplementation (5.93 vs 1.88 ml/min 1.73 m2; P < 0.0001). Patients supplemented with bicarbonate were significantly less likely to experience rapid progression 

Nutritional parameters improved significantly with bicarbonate supplementation, which was well tolerated. This study demonstrates that bicarbonate supplementation slows the rate of progression of renal failure to ESRD and improves nutritional status among patients with CKD.

Contraindications of bicarbonate therapy

NaHCO3 is contraindicated in patients with metabolic or respiratory alkalosis and in those with hypocalcemia in whom alkalosis may induce tetany, hypochloremia, and hypokalemia. It should also be used with caution in patients with chronic obstructive pulmonary disease, because alkalization can reduce the sensitivity of the respiratory regulatory center.

4) What was the indication for dialysing her and what was the crucial factor that led to the decision to dialyze her on the third day of admission? 

On day 3 - She had complains of SOB with a Blood pressure as high as 170/90mmhg and

Her chest xray shows Kerley B lines. The patient had anuria. - The patient was in pulmonary edema  - The fluid overload had to be relieed by dialysis

Refractory acidosis is also an indication for hemodialysis,

5) What are the other factors other than diabetes and hypertension that led to her current condition? 

With progression of age, the GFR also declines

Toxin intake such as tobacco since 8 years is also an added factor

A more detailed drug history, whether she was on any NSAIDS , any associated features suggestive of vasculitis would've been helpful.

7) How and when would you evaluate her further for cardio renal HFpEF and what are the mechanisms of HFpEF in diabetic renal failure patients?

Image from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737277/#:~:text=CKD%20is%20an%20independent%20risk,et%20al.%2C%202017).

The  co-existence of HFpEF and CKD is  due to common underlying comorbidities, such as hypertension, dyslipidemia and diabetes. Macrovascular changes accompanying CKD, such as hypertension and arterial stiffening, have been described to contribute to HFpEF development. Furthermore, several renal factors have a direct impact on the heart. These factors include activation of the renin-angiotensin-aldosterone system,  anemia, hypercalcemia, hyperphosphatemia and increased levels of FGF-23, and uremic toxins.

8) What are the efficacies over placebo for the available therapeutic options being provided to her for her anemia? 

A double blinded randomized placebo controlled multi-centre study on assessing quality of life & exercise capicity to recombinant human erythropoeitin 

 P - 118 Patients receiving haemodialysis aged 18-75 with haemoglobin concentrations less than 90 g/l, no causes of anaemia other than erythropoietin deficiency, and no other serious diseases. 

I -Patients were randomised to three groups to receive placebo (40) , erythropoietin to achieve a haemoglobin concentration of 95-110 g/l ( 40), or erythropoietin to achieve a haemoglobin concentration of 115-130 g/l (n = 38). 

Erythropoietin was given intravenously thrice weekly, initially at 100 units/kg/dose. The dose was subsequently adjusted to achieve the target haemoglobin concentration. 

All patients with a serum ferritin concentration less than 250 micrograms/l received oral or intravenous iron for one month before the study and as necessary throughout the trial. 

RESULTS--The mean  haemoglobin concentration at six months was 74 (12) g/l in patients given placebo, 102 (10) g/l in those in the low erythropoietin group, and 117 (17) g/l in those in the high erythropoietin group. 

Compared with the placebo group, patients treated with erythropoietin had a significant improvement in their scores for fatigue, physical symptoms, relationships, and depression on the kidney disease questionnaire and in the global and physical scores on the sickness impact profile. The distance walked in the stress test increased in the group treated with erythropoietin, but there was no improvement in the six minute walk test, psychosocial scores on the sickness impact profile, or time trade off scores. There was no significant difference in the improvement in quality of life or exercise capacity between the two groups taking erythropoietin. Patients taking erythropoietin had a significantly increased diastolic blood pressure despite an increase in either the dose or number of antihypertensive drugs used. Eleven of 78 patients treated with erythropoietin had their sites of access clotted compared with only one of 40 patients given placebo. 

CONCLUSIONS--Patients receiving erythropoietin were appreciably less fatigued, complained of less severe physical symptoms, and had moderate improvements in exercise tolerance and depression compared with patients not receiving erythropoietin. At the doses used in this trial there was a higher incidence of hypertension and clotting of the vascular access in patients treated with erythropoietin.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1662387/#:~:text=CONCLUSIONS--Patients%20receiving%20erythropoietin,with%20patients%20not%20receiving%20erythropoietin

What is the utility of tools like the CKD-AQ that assess the frequency, severity, and impact on daily activities of symptoms of anemia of CKD? 

CKD AQ is a 28-week, Double-blind, randomized placebo-controlled, multi-center, Study

28 week trial on Daprodustat vs placebo in non haemodialysis renal failure 

The trial is still ongoing and the results haven't been published yet. 

10) What is the contribution of protein energy malnutrition to her severe hypoalbuminemia? What is the utility of tools such as SGA subjective global assessment in the evaluation of malnutrition in CRF patients? 

Subjective Global Assessment (SGA) is a tool that uses 5 components of a medical history (weight change, dietary intake, gastrointestinal symptoms, functional capacity, disease and its relation to nutritional requirements) and 3 components of a brief physical examination (signs of fat and muscle wasting, nutrition-associated alternations in fluid balance) to assess nutritional status

A cross sectional study was conducted at SRN Hospital, Allahabad, Uttar Pradesh, India on patients attending Nephrology Unit from July 2014 to May 2015.

P - The nutritional status of 100 patients was evaluated using dietary recall, anthropometry, biochemical parameter and subjective global assessment. There were 67 males and 23 females.

I- Subjective global assessment was done using 7 variables derived from medical history and physical examination. Each variable was scored from 1-5 depending on the severity.

 Out of 100 patients 29% were mildly malnourished, 64% were moderately malnourished and 7% were severely malnourished. The age, triceps thickness, serum urea and cholesterol were correlated with the malnutrition score

The subjective global assessment can be used reliably to assess the malnutrition in the patients of chronic kidney disease and hence useful in prognostication of disease and is a convenient bedside tool. 

https://www.ijmedicine.com/index.php/ijam/article/view/269

2) The second patient differs from the first as the second patient does have urine output but reduced and is also complaining of dribbling of urine

Probably Prerenal AKI with Bun : creatinine ratio >20:1 and he could be having an underlying ckd due to his long standing Hypertension and diabetes with alcoholism. 

He has responded well to diuretics and fluid therapy

His usg abdomen findings show increased echogenicity of the kidneys, the kidneys size haven't reduced.