Anasarca

I’ve been given this case as an assignment. 

(https://alekyatummala.blogspot.com/2020/09/45-yr-female-with-anasarca.html?m=1)

Case 1

Here,

A 45 year old female presented with the complaints of

• Pedal edema since 5 days - pitting type
• Abdominal distension
• Facial puffiness
• No urine output since 3 days
• SOB at rest
• Palpitations

She has HTN since 1 year and a diabetic since 5 years. She has on and off pedal edema since 6 months which aggravated on walking and relieved on taking rest for which she was advised to reduce the fluid intake at a local hospital.

On day 1,

Her blood pressure was 180/80mm Hg.

Abdomen distended.

Pitting type pedal edema.

On RFT Urea, Creatinine, Uricacid levels were found elevated - KIDNEY DISEASE

Reduced serum calcium, potassium, sodium.

CBC showed a microcytic, hypochromic anemia - IRON DEFICIENCY ANEMIA

Complete urine examination showed the presence of Albumin 

ABG showed a reduced PH and pCO2 with increased pO2 - METABOLIC ACIDOSIS

Blood sugar was found to be within normal limits.

But an ulcer was found on the right sole might probably suggest a poop glycemic control.

A provisional diagnosis of DIABETIC NEPHROPATHY with METABOLIC ACIDOSIS with IRON DEFICIENCY ANEMIA was made.

Treatment :

NaHCO3 inj

POTCHOLR syp 

OHA , Anti hypertensives

On day 2,

She had pain abdomen and she didn’t pass urine.

Her blood pressure was under control.

Serum albumin was found to be 2g/dl.

On day 3,

She developed severe SOB with metabolic acidosis.

Blood pressure was 170/90mm Hg

2D echo was done, which revealed a diastolic dysfunction with a trivial mitral and tricuspid regurgitation.

Dialysis was done.

Chest X-ray 

Treatment was continued by adding 

OROFER - for iron deficiency anemia 

Inj Erythropoietin 

SHELCAL - vitamin D and calcium deficiency.

The SOB might attribute to heart failure because of microvascular changes.

On day 4,

Chest X-ray 

Dialysis was done

Later she developed pleural effusion

DIABETIC NEPHROPATHY 

Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy. 

First, mesangial expansion is directly induced by hyperglycemia, perhaps via increased matrix production or glycation of matrix proteins. 

Second, thickening of the glomerular basement membrane (GBM) occurs. 

Third, glomerular sclerosis is caused by intraglomerular hypertension (induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli). 

Hyperglycaemia - causing hyperfiltration and renal injury

Advanced glycation products

Activation of cytokines might be the etiology behind it.

(https://emedicine.medscape.com/article/238946-overview#a6)

CARDIORENAL SYNDROME 

Type 1 - CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. 

Type 2 - CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. 

Type 3 - CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). 

Type 4 - CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. 

Type 5 - CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. 

There is a possibility of type 4 cardiorenal syndrome in this case.

(https://www.onlinejacc.org/content/52/19/1527)

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Questions 

1. Diagnosis :

Chronic kidney disease - Diabetic Nephropathy might be contributing to heart failure

CARDIORENAL SYNDROME type 4

2. Causes of :

Azotemia is the elevation of blood urea nitrogen. Perturbation in the process of urine formation prevents the final products of metabolic activity from the body to eliminate and hence cause Azotemia.

Anemia occurred as the diseased kidneys are not able to make enough Erythropoietin.

Hypoalbuminemia because of proteinuria.

Acidosis because of Impaired ammonia excretion, Reduced tubular bicarbonate reabsorption and Insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food.

3. Rationale of Bicarbonate treatment :

Alkali supplementation in metabolic acidosis due to CKD have shown beneficial effect in preventing the progression to ESRD.

NaHCO3 given orally supplies bicarbonate ions indirectly (exchange of one HCO 􏰀 ion for each H ion used in the reaction in the gastric lumen) and directly (absorption from gastrointestinal tract)

Replacement of sodium bicarbonate is beneficial in disorders associated with loss of sodium bicarbonate, such as diarrhea and renal tubular acidosis, but symptomatic therapy with sodium bicarbonate to correct metabolic acidosis per se in other settings has not been demonstrated to ameliorate clinical outcomes or mortality. Further, sodium bicarbonate supplementation fails to raise plasma pH or increases it only slightly in some patients affected with malignancy-associated lactic acidosis.

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

Contraindications :

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.

Acute conditions in which sodium bicarbonate therapy doesn’t improve outcomes -

Diabetic ketoacidosis

Lactic acidosis

Septic shock

Cardiac arrest

4. Indications of dialysis in this patient :

Anuria

Urea over 35 Mmol/l

Severe fluid overload

Metabolic acidosis

5. Factors that let to her current condition :

Her renal issues are multifactorial. Her current glomerular injury manifested in nephrotic proteinuria is due to diabetes and hypertension. 

She has been chewing tobacco since 8 years which might have caused endothelial injury and adverse cardiac and renal side effects.

Progressive kidney failure can be associated with a gradual decrease of renal and non-renal elimination of nicotine, and this increases the rate of nephrotoxicity. Also, the effects of heavy metals in tobacco like Cadmium (Cd), Mercury (Hg) and Lead (Pb), might be another possible mechanism for tobacco-induced renal damage. However, the mechanism by which tobacco chewing and smoking induces renal damage may be through enhancing the synthesis of free radicals may lead to alter the glomerular function leading to elevated the levels of urea and creatinine in tobacco chewers and smokers. 

(https://www.alliedacademies.org/articles/tobacco-chewing-and-smoking-risk-for-renal-diseases.html)

She might have taken NSAIDs that would have precipitated reduced renal perfusion.

Her current condition may also be precipitated by infections.

6. Expected outcomes :

Patients with diabetes and CKD have a lower quality of life and higher health care costs, and face the prospect of end-stage renal disease requiring dialysis. More importantly, this group has an extremely elevated cardiovascular risk and correspondingly reduced survival. Research over several decades has led to two important conclusions. First, progressive worsening of kidney disease is not inevitable in people with diabetes; it can be slowed or even stopped. Second, the elevated cardiovascular risk in this population can be significantly reduced through an aggressive approach to cardiovascular risk factor reduction.

Control of hypertension is of primary importance in patients with diabetic nephropathy. Current guidelines state that the BP goal in patients with diabetes is ≤130/80 mmHg.

Glycemic control is important in this population.

The RENAAL risk score for ESRD emphasizes the importance of identification of level of albuminuria, hypoalbuminemia, increased serum creatinine, and decreased hemoglobin level to predict the development of ESRD in patients with type 2 diabetes and nephropathy. Although albuminuria is a very strong predictor for ESRD, the contribution of serum albumin, serum creatinine, and hemoglobin level further enhances the prediction of ESRD. 

((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650765/))

(https://cjasn.asnjournals.org/content/1/4/761)

7. The patient should be evaluated for cardio renal HFpEF when she develops intermittent paroxysmal nocturnal dyspnea, orthopnea, dyspnea, fatigue, ascites, and dependent edema.

HFpEF as simply a disease of diastolic function to a reconceptualizing of it as more of a systemic disease, characterized by inflammation and microvasculature dysfunction with adverse sequelae in multiple organs, including, but not limited to, the heart.

Patients with diabetes mellitus were characterized by multimorbidity, left ventricular hypertrophy, impaired chronotropic reserve, and activation of inflammatory, pro-oxidative, vasoconstrictor, and profibrotic pathways. 

Both maximal (peak oxygen uptake) and submaximal (6-minute walk distance) exercise capacity were impaired in patients with diabetes mellitus, and hospitalization rates for cardiac or renal causes were increased.

(https://www.ahajournals.org/doi/full/10.1161/circulationaha.116.025957)

(https://www.sciencedirect.com/science/article/pii/S0085253819302765)

8. Efficacy of placebo over treatment :

Erythropoietin - The introduction of erythropoietin (Epo) in clinical practice, more than two decades ago, altered completely the management of patients with chronic kidney disease (CKD). 

The extensive use of Epo and its analogues (erythropoietin- stimulating agents, ESAs) for the purpose of anemia correction has succeeded in reduction of associated morbidity and improvement of functionality, exercise tolerance, cognitive function and overall quality of life. Moreover, significant reduction of cardiovascular (CV) morbidity and mortality has occurred. 

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208971/)

(https://cjasn.asnjournals.org/content/2/2/215)

(https://www.sciencedirect.com/science/article/abs/pii/S0272638689801490)

9. Contents of CKDAQ (chronic kidney disease Anemia Questionnaire)

Symptom/Impact	Number of Items
Frequency and severitya	14
Very tired	2
Low energy	2
Weak	2
Chest pain	2
Shortness of breath during activity	2
Shortness of breath while at rest	2
Difficulty concentrating	2
Severitya	1
Bruised skin (past month recall period)	1
Frequencya	1
Difficulty remembering things	1
Impact/ability to do activitiesb	5
Standing for long periods of time	1
Sleeping	1
Didn’t want to do anything	1
Need to take a break	1
Need to take a nap	1
Emotional impactc	2
Distress	1
Feel burdensome	1

The Chronic Kidney Disease and Anaemia Questionnaire (CKDAQ) is a 22-item GSK-developed PRO instrument to assess the association with quality of life of patients with chronic kidney disease and anaemia. This questionnaire went through linguistic validation into 71 languages, of which 30 were Asia-Pacific languages. The objective is to identify the challenges raised in performing linguistic validation in these languages; focusing on terminology specific to kidney disease and anaemia, grammatical structure, format, style and register.

(https://jpro.springeropen.com/articles/10.1186/s41687-020-00215-8)

10. Contribution of protein energy malnutrition to hypoalbuminuria:

Deficient protein intake results in the rapid loss of cellular ribonucleic acid and disaggregation of the endoplasmic reticulum–bound polysomes and, therefore, decreased albumin synthesis. 

Kwashiorkor, a severe form of protein-energy malnutrition, presenting in infants and children. They have low serum albumin levels due to a decreased supply of amino acids to the liver as well as other nutritional deficiencies, notably iron and zinc.

(https://www.ncbi.nlm.nih.gov/books/NBK526080/)

SGA in evaluation of malnutrition in CRF patients :

Nutritional assessment of patients with chronic kidney disease is a vital function of health care providers. 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.

Poor nutritional status due to protein-energy wasting (PEW) is a common complication associated with increased mortality in patients with chronic kidney disease (CKD) . Most nutritional markers used in clinical practice are influenced by CKD, co-morbidities or non-nutritional factors such as inflammation, overhydration, and protein losses.

PEW assessed by SGA was found to be an independent predictor of mortality. A range of non-composite nutritional markers could not adequately classify presence of clinically defined poor nutritional status, or explain the variation of SGA status, together with the finding that SGA is a robust prognosticator of clinical outcome, support the value of SGA as assessor of nutritional status in patients with CKD.

(https://pubmed.ncbi.nlm.nih.gov/15483778/)

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718431/)

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In a similar case, 

(https://bhavyayammanuru.blogspot.com/2020/09/aki-secondary-to-uti.html?m=1)

Case 2:

A 58 year old male presented with the complaints of :

• Reduced urinary output since 3 days associated with burning micturition.
• Anuria since 1 day
• Pain abdomen since 1 day
• Cough not associated with sputum
• Low grade continuous fever not associated with chills

He was a diabetic since 5 years and hypertensive since 8 months.

On examination, there was grade 2 edema which was tender and non pitting type.

Investigations showed slight hypokalemia and metabolic acidosis.

CBP showed normocytic normochromic anemia with raised total and neutrophil count and reduced RBC and lymphocyte count.

RFT was abnormal with high amounts of urea, Uric acid and creatinine.

Traces of albumin was found in the urine.

Distended bladder was found on ultrasound examination. Prostrate was normal.

LFT was abnormal with increase in total bilirubin, direct bilirubin, alkaline phosphate, reduced albumin.

This patient had fever and cough which suggests an infectious etiology. He also had an increase in WBC and neutrophil count. The clotting factors also seemed to decrease as aPTT was slightly increased. 

Also justifies abnormal LFT.

Absence of any other features of sepsis as in tachycardia, hypotension raises a doubt about the etiology being sepsis.

Post renal cause is suspected because of the history of pain abdomen and burning micturition and distended urinary bladder on examination.

Patient might have had the similar etiology as the previous one as in diabetic nephropathy.

Treatment :

PIPTAZ - antibiotic

LASIX - diuretic

AMLOG - anti hypertensive 

HAI - anti diabetic

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Questions :

1. Differences in diagnosis, therapy and outcomes :

The diagnosis in the first case is diabetic nephropathy leading to cardiorenal syndrome type 4.

In the second case a pre renal AKI is suspected for which the etiology might be sepsis or diabetes leading to hypertension. We couldn’t rule out a post renal cause either.

The first case presented with metabolic acidosis and anemia so we used Erythropoietin and iron supplements along with a trial of bicarbonate.

In the second case we were suspecting an infectious pathology so an empirical antibiotic therapy was started.

Outcome in the second case might be better than the first one if appropriately treated.

2. Diagnosis shared for second case :

The shared diagnosis for second case might be true as being prerenal AKI - etiology not mentioned.

Postrenal AKI isn’t ruled out either.

3. Ultrasound findings of both kidneys :

The kidneys aren’t symmetrical in case 2. There seems to be a slight reduction in the size of left kidney - might indicate fibrosis. The question to as weather this is the reason for the kidney failure or just an Insignificant incidental finding remains.

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